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Showing 57 results for Leukemia
The diagnostic value of CD14 and CD64 expression in differential diagnosis of monoid subtype of acute myeloid leukemia
M. Nikougoftar , M. Aghaeipour , A. Tabatabaian , Sh. Vaeli , V. Fallah Azad , M. Maghsudlu , F. Atashrazm ,
Volume 2, Issue 3 (3-2005)
Abstract

  Abstract

  

 Background and Objectives

  Although the French-American-British (FAB) Classification system is the basis for the diagnosis and treatment of AML, it has its own limitations. During recent years immunophenotyping by flow cytometry is widely used for the identification of AML'S subtypes. Immunophenotyping has been especially helpful in discrimination of AML with monocytic differentiation (M4-M5) from nonmonocytic subtypes (M0- M1- M2- M3- M6- M7). However several studies have indicated that CD14 mostly is negative when applied to leukemias with monocyte differentiation.

  

  Materials and Methods 

  Some studies have shown that CD64 (FC g RI) is an early and specific myelo-monoid marker. In this study we evaluated CD14 and CD64 antibodies to identify cells of monocytic lineage in 216 cases of AML who were referred to IBTO flow cytometry laboratory. These monoclonal antibodies prepared by DAKO company and were conjugated with Phyco Erythrin. The samples were analysed by Epics-x1 Flow cytometer. The markers were considered positive if 20% or more of the cells expressed it. The Chi-square test was also used in SPSS software.

 

 Results

  Results revealed that CD64 was highty specific (88%) and sensitive (67%) and CD14 was highty specific (96%) but not sensitive (31%) with >95% confidence rate. These results are compatible with other studies.

  

 Conclusions

  Finally because of high sensitivity of CD64, it should be considered in all of immunophenotyping protocols as a sensitive and specific marker for monoid cells.

  

  

Key words : Acute leukemia, FAB, Immunophenotyping, Flow cytometry, Acute myeloid leukemia, Acute monocytic leukemia, CD14, CD64.
Detection of N-RAS gene mutations in codons 12, 13 and 61 in patients with acute myeloid leukemia
Y. Mortazavi, M. Behzadi Fard, A.a. Pourfathollah, S. Kaviani, A.a. Feizi,
Volume 4, Issue 1 (3-2007)
Abstract

  Abstract

 Background and Objectives

 Acute myeloid leukemia (AML) comprises a heterogenic group of malignant disorders involving cell maturation arrest at an undifferentiated stage in bone marrow. Activation of N-RAS proto-oncogene due to point mutations plays a major role in AML malignancy. Since there was no report on the frequency of N-RAS gene mutations in Iranian AML patients, therefore, we decided to determine its frequency and compare the results with age, sex and FAB subtypes.

 

 Materials and Methods

 In this descriptive study, 60 de novo AML patients from Tehran Shariati hospital, hematology-oncology and bone marrow transplantation center were screened for the mutations of N-RAS gene at codons 12, 13 and 61. DNA was extracted from peripheral blood samples before the start of chemotherapy. The above mentioned codons were amplified by PCR and analyzed by restriction endnuclease enzymes.

 

 Results

 We were able to detect mutations in 12 out of 60 (20%) patients. Most of the mutations were detected in men with an age over 40 years old. The frequency of mutations for codons 12, 13 and 61 were 15% ,11.6% and 5% respectively. Most of the mutations (33.3%) were found to happen in AML-M4 FAB subtype. We could not detect any mutation in AML-MO, M6 and M7.

 

 Conclusions

 We detected mutations in 20% of our AML patients. In general, the frequency of the mutations we found was in agreement with the results of other studies. However, a study with more patients and a wider range of age using a combination of PCR-RFLP and direct gene sequencing is highly recommended.

 

 Key words : Acute myelocytic leukemia, Mutation. PCR


Analysis of telomere length changes in chronic and blastic phases of chronic myelogenous leukemia
N. Bagheri, Dr. Y. Mortazavi, Dr. H. Ghafari, Dr. K. Alimoghadam, Dr. A.a. Pourfatoullah, N. Shayan, Dr. A. Gavam Zadeh,
Volume 5, Issue 1 (3-2008)
Abstract

  Abstract

 Background and Objectives

 In the mammalian cells, there is a relationship between telomere length and both cancer and senescence. Progressive telomere shortening has a role in genomic instability and has been reported in a wide range of human cancers as well as in transformation and progression to hematologic malignancies. Chronic myelogenous leukemia (CML) has different stages in the process of its progression. In this study, we examined the telomere length changes in peripheral blood leukocytes of CML patients in chronic (CP) and blastic phases (BP).

 

 Materials and Methods

 In this descriptive study, we examined the telomere length in 21 CML patients (14 in chronic and 7 in blastic phases) having reffered to Hematology–Oncology and BMT Research Center of Shariati Hospital since March 2004 using Southern blot analysis the results were then compared with age-adjusted normal controls. Data were analyzed through logestic regression and Anova.

 

 Results

 At the time of diagnosis, 71.43% of chronic phase patients had a shortened TRF compared to normal age-adjusted individuals. The mean telomere length values in chronic and blastic phases were 6.98±1.26 kb and 4.81±1.06 kb, respectively it showed significant telomere length reduction in age-adjusted normal controls. Moreover, the mean telomere length values in BP-CML showed significant statistical differences as compared to CP-CML. Mean values of telomere length reduction in CP-CML and BP-CML as compared with normal age-adjusted control group were 3.31±1.38 kb and 5.27±0.9 kb, respectively.

 

 Conclusions

 The significant statistical differences in mean telomere length of CP-CML and BP-CML as compared with age-adjusted normal controls and the apparent differences of TRF in chronic and blastic phases can be useful in prediction of phase of disease progression.

 �

 Key words : Chronic myelogenous leukemia, Telomere, Southern blot

 


Multiple drug resistance in acute myelocytic leukemia/acute lymphocyte leukemia patients and MDR evaluation
Dr. K. Ali Moghadam, Dr. M. Alami Samimi, A. Ashori, Dr. M. Toutounchi, Dr. M. Farhadi Langroudi, Dr. F. Nadali, Dr. M. Iravani, S.a. Mousavi, Dr. A. Khodabandeh, Dr. M. Jahani, Dr. A. Ghavamzadeh,
Volume 5, Issue 1 (3-2008)
Abstract

  Abstract

 Background and Objectives

 Drug resistance is a common cause of treatment failure in malignant disorders especially hematological malignancies. Overexpression of P-glycoprotein (pgp) is the most common cause of drug resistance. Studies on the importance of pgp are controversial that is attributed to the lack of a standard method for pgp assay and the lack of consistency with clinical data. The aim of this study is Multiple drug resistance (MDR) evaluation according to pgp expression in leukemic cells at the beginning of treatment, and prediction of responses to treatment, relapse or death.

 

 Materials and Methods

 Between June 2001 and May 2006, we studied 185 leukemic patients. Diagnosis was performed on each case via morphology, based on immunotypes, and by cytogenetic method pgp expression was also evaluated by flowcytometry. For pgp evaluation, we collected peripheral blood or bone marrow samples in EDTA. Then, patients went under treatment by standard protocols and their responses to treatment were observed. Patient follow ups for response to treatment, complete remission, resistance to induction, relapse or death were conducted. Finally, clinical data were compared with laboratory results. Mann-Whitney, kruscal-valis, kaplan-meier, and chi-square tests were used for data analysis.

 

 Results

 From 185 patients with the median age of 28.5 years (within the age range of 11-76), 128 patients showed AML and 57 ALL. 62% were male and 38% female. Pgp expression showed no significant correlation with age, sex, type of leukemia, and white blood cells count. There was no significant association between pgp expression and AML subtype. Two-year Overall Survival (OS) and Disease Free Survival (DFS) were 63% and 42% respectively. DFS showed significant correlation with pgp in ALL and non-M3 subtype of AML (P=0.024).

 

 Conclusions

 Expression of pgp would be a prognostic factor for relapse prediction and might be important in treatment planning.

 �

 Key words : Multiple drug resistance, P-Glycoprotein, Acute myelocytic leukemia, Acute lymphocytic leukemia

 


BCR-ABL fusion transcript detection in Iranianpatients with chronic myeloid leukemia
S.h. Ghaffari, M. Yaghmaie, K. Alimoghaddam, A. Ghavamzadeh, M. Jahani, S.a. Mousavi, M. Irvani, B. Bahar, E. Baibordi,
Volume 5, Issue 2 (8-2008)
Abstract

  Abstract

 Background and Objectives

 A specific chromosomal abnormality, the Philadelphia chromosome (Ph), is present in more than 90% of CML patients. The aberration results from a reciprocal translocation between chromosome 9 and 22, creating a BCR-ABL fusion gene. Major forms of BCR-ABL fusion are b3a2, b2a2, and e1a2. Less common fusion genes are b3a3 or b2a3 (p203) and el9a2 (p230). The aim of this study was to set up a multiplex RT-PCR assay and determine the frequency of different fusion genes in 75 Iranian patients with CML.

 �

 Materials and Methods

 In this experimental study, peripheral blood samples from 75 adult Iranian CML patients were analyzed by multiplex RT-PCR to detect different types of BCR-ABL transcripts of the t(9:22).

 �

 Results

 All of the examined cases were positive for some type of BCR/ABL rearrangement. The majority of patients (82.6%) expressed one of the P210 BCR-ABL transcripts (b3a2, 62% and b2a2, 20%), while the remaining showed either one of the transcripts of b3a3, b2a3, ela2 or coexpression of b3a2 and b2a2. The rate of coexpression of the b3a2 and b2a2 was 5%.

 

 Conclusions

 It is possible to detect rare fusions other than common ones through multiplex method. In Iranian CML patients, b3a2 was three times more frequent than b2a2 shown to be higher as compared with other studies. Probably, the kind of fusion is of clinical importance and helps us in understanding t(9:22) leukemic cells pathogenesis.

 �

 Key words : Chronic myeloid leukemia, RT-PCR, Philadelphia chromosome

 


Cytogenetic study of prognostic determinants in children with acute lymphoblastic leukemia
Sh. Nazari, A. Shafiei, F. Abdollah Gorji,
Volume 5, Issue 2 (8-2008)
Abstract

  Abstract

 Background and Objectives

 Acute lymphoblastic leukemia though the most frequent malignancy in children has well responded to medical treatment as compared with other types of malignancies in recent years. In addition to age, sex and number of white blood cells, genetic survey has been one of the prognostic determinants. This research has been carried out on children diagnosed after being referred to Mofid Children Hospital during a period of three years. This study aims at determining the factors effective on prognosis of lymphoblastic leukemia with an emphasis on patient acute karyotype.

 

 Materials and Methods

 Out of 102 patients with the diagnosis of acute lymphoblastic leukemia being referred to this hospital between 1990-2002, 74 (within the age groups varying from 6 months to 13 years old) underwent cytogenetic test out of the latter 28 were excluded. These 74 were classified according to their WBC count and age into high (42 cases) and low risk groups (32 cases). Then, the results were analyzed and compared according to the subfactors such as flowcytometry, age, sex, and blood cell count (WBC, hemoglobin and platelet) both in high and low risk groups.

 

 Results

 From 74 cases under study, flowcytometry showed that 64 (86.5%) suffered from leukemia type pre B cell out of the latter 38 (59.4%) based on the number of white cells were placed in the low-risk group. In cytogenetic survey, 34 (45.9%) patients had normal karyotype, 16 (21.6%) had abnormality of chromosome number, and 14 (19%) abnormality of chromosomal structure. No conclusion could be drawn from cytogenetic test conducted on the remaining 10 cases. Comparison of the two groups of high and low risk showed no significant differences. From gender point of view, number of boys was considerably higher than girls in the low risk group (61.9% vs. 39.1%). But as far as karyotype was concerned, there were no differences between the two groups.

 

 Conclusions

 Regarding the research findings, there was no significant difference between the two groups from genetic disorders point of view. Accordingly, we can conclude that age and number of WBC by themselves are not suitable preliminary factors for prognosis and genetic determination in genes domain. So, it seems necessary for a similar research at a larger scale to be conducted in which prognostic determinants are complied with disease trend.

 �

 Key words : Acute lymphoblastic leukemia, Cytogenetic, Prognosis

 


Nucleostemin gene expression in acute promyelocytic leukemia in relation to arsenic trioxide and cell differentiation
Dr. F. Nadali, Dr. K. Ali Moghadam, Sh. Rostami, Dr. A. Ghavamzadeh,
Volume 6, Issue 1 (5-2009)
Abstract

  Abstract

 Background and Objectives

 Acute Promyelocytic Leukemia (APL) is one subtype of acute myeloblastic leukemia it responds to differentiation using All-Trans Retinoic Acid (ATRA). Recently, arsenic trioxide (As2O3) has been added to this method. The cellular mechanism of differentiation therapy by arsenic is not yet clear. We decided to study the relationship between cell differentiation using arsenic trioxide and nucleostemin gene as a proliferation marker.

 

 Materials and Methods

 In this descriptive study, we treated NB4 cell (a cell line in APL) with 0.5, 1, and 2 µM of arsenic trioxide in 6 well plates for five days. Then, cellular differentiation was assessed by flowcytometry for CD11b. Nucleostemin gene expression was also assessed by Real Time PCR.

 

 Results

 According to the results, cell proliferation has occurred by 0.5 µM arsenic trioxide and no differentiation was observed during 10 days of culture. With 1 µM concentration of arsenic, CD11b has raised from 5.2% to 13.6% during five days of culture (p < 0.001). Morever, 1 µM of arsenic caused decrease in nucleostemin gene copy number from 130 to 70.

 

 Conclusions

 According to the results, 1 µM of arsenic has increased CD11b in the cells and caused a partial differentiation during five days of culture. Increase in CD11b marker has also been associated with decrease in nucleostemin gene expression as a proliferation marker.

 �

 Key words : Leukemia, Promyelocytic, Acute, arsenic trioxide, RT- PCR�


L-Asparginase effect with 6000U/m2 on lipid profile in children with acute lymphoblastic leukemia
Dr. Mt. Arzanian, Dr. A. Eghbali, Dr. S. Alavi, Dr. B. Sh. Shamsian, Dr. F. Malek, Dr. E. Azargashb,
Volume 6, Issue 2 (8-2009)
Abstract

  Abstract

 Background and objectives

 One of the major etiologies of lipid disorders in malignancies is the use of chemotherapy drugs, the most important of which is L-Asparginase. Studies in different centers with high dosages of L-Asparginase demonstrated different results. The aim of this study is to evaluate the effect of L-Asparginase at a dose of 6000 U/m2 on lipid profile in Iranian children with newly diagnosed acute lymphoblastic leukemia in Mofid Children Hospital of Tehran .

 

 Materials and Methods

 We performed a nonrandomized trial in which all children with newly diagnosed acute lymphoblastic leukemia (ALL) aged <15 years participated. Every case serves as his/her own control. The cholesterol, triglyceride (TG), HDL, LDL, VLDL, APOA, APOB and LPa were evaluated in three stages: before, during and 2 months after treatment with L-Asparginase after which the results were compared.

 

 Results

 In our study, 82 newly ALL diagnosed patients with the mean age of 6 years (within the age range of 0.12-14 and SD of 3.5) were evaluated. Mean seum level of TG in pretreatment stage was 163.9 mg% and during treatment with L-Asparginase 123 mg% demonstrating significant decline in TG serum level after administration of L-Asparginase (p=0.002). Mean serum level of cholesterol before administration of L-Asparginase was 151mg% and during treatment 140 showing no statistically significant difference (p= 0.061). LPa level in pretreatment phase was 24mg% and during treatment 14 showing a statistically significant difference (p= 0.0001).

 

 Conclusions

 L-Aspar resulted in decline in TG serum level and increase in HDL though with no significant difference in cholesterol level. Overall, L-Asparginase even at a dose of 6000U/M2 does not raise blood level of triglyceride and cholesterol.

 �

 Key words : Leukemia, Lymphoblastic, Acute, L-Asparagine, children


Terminal deoxynucleotidyl transferase expression in acute myeloblastic leukemia
Dr. S.h. Maljayi, Dr. A. Khakbaz, Dr. A. Knikanfar,
Volume 6, Issue 3 (10-2009)
Abstract

  Abstract

 Background and Objectives

 Many studies have provided conclusive evidence for the existence of terminal deoxynucleotidyl transferase (TdT) positive cases in some subgroups of AML. In approximately a half of studies TdT expression is correlated with poor prognosis. The incidence of TdT positive cases in patients varies in a wide range. This study was performed to determine the incidence of TdT expression in AML patients in our community and its positivity in morphologic subgroups at different sex and age groups.

 

 Materials and Methods

 In this study, 101 AML patients having referred to the Hematology and Oncology Center of Tabriz University of Medical Sciences were included. Data about FAB subgroups, sex, age and flowcytometry of patients were analyzed in SPSS software.

 

 Results

 TdT positive cells were detected in 24 patients (23.7%) two thirds of whom male. The median age of TdT positive patients was 30 years versus 40 in TdT–negative patients. Out of the 24 patients in the former, the age of 9 patients was under 20 years. TdT positivity was significantly associated with FAB M2 cases with 39% of whom being TdT-positive while this percentage in other FAB classes is calculated to be 15.3% (p= 0.004).

 

 Conclusions

 The TdT expression in AML is correlated with age. It is more common in patients under the age of 20. Although TdT expression is more common in M1/M2 AML cases, it also can occur in other FAB subtypes of AML.

 �

 Key words : Leukemia, Myeloid, Acute, Deoxynucleotidyl Transferase, Flow Cytometry�

 


Detection and assessment of the frequency of NPM1 and FLT3 ITD mutations in acute myeloid leukemia patients
V. Pazhakh, Dr. F. Zaker, Dr. K. Ali Moghadam, F. Atashrazm,
Volume 6, Issue 3 (10-2009)
Abstract

  Abstract

 Background and Objectives

 NPM1/Nucleophismin/B23 is a phosphoprotein with high expression in the proliferating cells. NPM1+AMLs are also frequently associated with FLT3 ITD mutations. The purposes of this study were to assess the frequency of NPM1 and FLT3 ITD mutations among Iranian AML patients and their correlation with FAB subtypes of AML.

 

 Materials and Methods

 Bone marrow and peripheral blood samples of 131 AML patients were randomly collected, and their DNA was then extracted. Afterwards, PCR was applied to the fragment of NPM1 gene with specific primers. PCR products were electrophoresed using CSGE method. In the end, the positive samples were sequenced to confirm the presence of NPM1 mutations. Furthermore, FLT3 ITD positive cases were screened using PCR and 2.5% agarose gel electrophoresis.

 

 Results

 Out of 131 patients, 23 (17.55%) (CI 95% = 0.107-0.244) were known to have NPM1 gene mutations. The highest frequency was among the subtypes of M4 (30.4%), M3 (21.7%), and M5 (13%). Also, 21 samples (16.03%) (CI 95% = 0.092-0.229) had FLT3 ITD mutations with 8 cases being NPM1 positive and other 13 NPM1 negative.

 Conclusions

 NPM1 mutations are more frequent in monocytic subtypes (M4, M5). High frequency rates of NPM1 in M3 subtypes and allele D mutations in all subtypes together with the high degree of association between occurrence of NPM1 and FLT3 ITD mutations could be considered as interesting findings of the study (p=0.012).

 �

 Key words : Leukemia, Myeloid, Acute, PCR, Electrophoresis, Agar Gel

 


Methylenetetrahydrofolate reductase polymorphisms and susceptibility to childhood ALL
F. Atashrazm, Dr. F. Zaker, Dr. M. Aghaeipour, Dr. V. Pazhakh,
Volume 6, Issue 4 (1-2010)
Abstract

  Abstract

 Background and Objectives

 Genetic variations and mutations are of the etiological factors leading to leukemia. Among these genetic alterations, polymorphisms are present on gene surfaces of some critical molecules. The aim of this study was to assess individual and/or combined role of these two polymorphisms (C677T and A1298C) in resistance against pediatric acute lymphoblastic leukemia. Moreover, the frequency rate of these important polymorphisms has not been reported in Iran so far and the present study is the first attempt to this end.

 

 Materials and Methods

 Using PCR and RFLP analyses, we studied the prevalence rate of the C677T and A1298C Methylenetetrahydrofolate (MTHFR) genotypes in 103 pediatric ALL patients and 160 age-sex matched control patients. The data were analyzed with Hardy-weinberg and Chi-square by SPSS 16.

 �

 Results

 No significant association between two common polymorphisms of MTHFR or combination of polymorphisms with the risk of ALL was observed. The study also showed the high prevalence of A1298C which was significantly higher than that reported for most Asian population (40.67% in our study versus 17-19% in Asian). It is proved that C677T prevalence pattern is similar with those in most Asian populations .

 

 Conclusion

 Our findings suggest that the MTHFR C677T and A1298C gene variants do not have a major influence on the susceptibility to pediatric ALL. But despite the absence of any significant association, the frequency of MTHFR 677TT was lower among patients than general population which may support previous evidence about its protective effect against ALL.

 

  Key words : Polymorphism(Genetic), Methylene Tetrahydrofolate Reductase, Lymphoblastic Leukemia, Acute


The effect of arsenic trioxide treatment on mitochondrial apoptotic gene expression in acute promyelocytic leukemia cell line
M. Sharifizadeh, Dr. M. Hashemi, M. Momeny, Dr. K. Alimoghaddam, Dr. A. Ghavamzadeh, Dr. H. Ghaffari,
Volume 7, Issue 3 (8-2010)
Abstract

  Abstract

 Background and Objectives

 Acute promyelocytic leukemia (APL) is one of the most malignant forms of acute leukemia with a fatal course of only weeks which represents 10-15% of AML in adults. Arsenic trioxide as a single agent factor (without chemotherapy) is the treatment of choice for APL patients it induces cell death through apoptosis but the mechanism by which arsenic targets apoptosis and dramatically affects gene expression remains poorly understood. Since arsenic is used as first line treatment in Iran, it is worth investigating its effect on expression of genes involved in APL.

 

 Materials and Methods

 In this descriptive study, to understand the underlying mechanisms of cell death induction by arsenic, we treated NB4 cell line in a dose and time dependent manner. Extracting RNA and synthesis of cDNA, gene expression of apoptotic genes in mitochondrial pathway including caspase3, Mcl-1 and Bcl-2 was analyzed through Real-Time PCR.

 

 Results

 Our findings showed that As2O3-induced cell death was paralleled by reduced expression of the antiapoptotic protein Bcl-2 but the expression of Caspase3 and Mcl-1 did not change after arsenic treatment.

 

 Conclusions

 These results suggest that changes in Bcl-2 gene expression may be one of the mechanisms of action of arsenic in induction of apoptosis, while Caspase3 and Mcl-1 gene expression are not affected by arsenic at the transcriptional level.

  

 Key words : Promyelocytic Leukemia, Acute, arsenic trioxide, Apoptosis, Caspase 3, bcl-2 Genes 

 


Expression analysis of Survivin gene in acute promyelocytic leukemia at diagnosis and after treatment
Dr. M.r. Nouri Dalouyi, Dr. M. Zaki Dizaji, S. Khavandi, Sh. Rostami, M. Yaseri, Dr. K. Alimoghaddam, Dr. A. Ghavamzadeh, Dr. H. Ghaffari,
Volume 8, Issue 1 (3-2011)
Abstract

  Abstract

 Background and Objectives

 Survivin (SVV) is an inhibitor of apoptosis. Its expression rises in most cancer types and is associated with resistance to chemotherapy, increased recurrence, and decreased patient survival. In this study, the expression of SVV gene was analyzed in APL(Acute Promyelocytic Leukemia) patients.

 

 Materials and Methods

 In this case-control study, the blood samples of 50 patients were collected in three groups diagnosis, remission, and recurrence. Then, SVV gene expression was studied using absolute quantitative real time PCR. The data were analysed with SPSS version 17, Kruskal-Wallis and Tukey tests.

 

 Results

 For the first time, this study demonstrated that SVV overexpressed significantly in APL patients compared with the control (Mean ± SD 910.5 ± 699) (p <0.01). This overexpression was seen both in diagnosis (4981.4 ± 4112.2) and recurrence groups (4584.2 ± 5133.6) (both p<0.01) . After arsenic trioxide therapy (ATO) the SVV expression declined significantly as compared to the diagnosis group (p<0.01).

 

 Conclusions

 Findings indicate that SVV may have a role in survival of APL cells and induction of apoptosis by decreasing SVV expression can be a probable mechanism of ATO. This study indicates that the SVV may be used as a biomarker in APL patients during the course of the disease.

 


Cerebral venous throbosis in a child with acute Lymphoblastic Leukemia and G20210A mutation of prothrombine gene during treatment
Dr. P. Eshghi, Dr. A. Amin Asnafi,
Volume 8, Issue 2 (5-2011)
Abstract

  Cerebral venous thrombosis in a child with Acute Lymphoblastic Leukemia and G20210A mutation of prothrombine gene during treatment

 

 

 Eshghi P.1, Amin Asnafi A.1

 

 

  1 Shahid Beheshti University of Medical Sciences,Tehran,Iran

  

 

 

  

  Abstract

 Background and Objectives

 Cerebral vein thrombosis is a relatively rare but important complication during treatment of Acute Lymphoblastic Leukemia(ALL) in children.

 

 Case

 A 12 year old boy with pre-B ALL during the consolidation phase of treatment with BFM protocol was admitted with severe headache imaging study showed cerebral venous thrombosis in left sigmoid and lateral sinuses. Diagnostic evaluation revealed heterozygot mutation in G20210A prothombin gene.

  

 Conclusions

 Some hereditary hypercoagulability states such as prothrombin G20210A heterogeneity, play an important role in childhood thrombotic events during treatment of hematologic malignancy with medications such as L-asparginase. So venous thrombosis prophylaxis in this situation should be considered.

  

 Key words : Leukemia, Venous Thrombosis, Mutation, Prothrombin 

 Sci J Iran Blood Transfus Org 2011 8(2): 143-148


Association of C609T and C465T polymorphisms of NQO1 gene with AML
A. Safaei, Dr. F. Zaker, H. Sharafi, Dr. M. Hashemi, Dr. P. Yaghmaei, M. Abdolahzadeh,
Volume 8, Issue 3 (8-2011)
Abstract

  Abstract

 Background and Objectives

 Many studies have demonstrated that polymorphisms of NQO1 including C465T and C609T are associated with increased risk of acute myeloid leukemia(AML). Our aims are to assess incidence of these polymorphisms in Tehran patients and study the influence of low activity of NQO1 in AML.

 

 Materials and Methods

 In this case-control study, we used PCR and RFLP analyses to study the prevalence of C609T NQO1in 140 patients, and C465T NQO1 in 124 patients there was also a control group of 80 being age-sex matched. We calculated odd ratio with SPSS 16 to examine if these polymorphisms are associated with AML.

  

 Results

 No significant association between the two common polymorphisms of NQO1 and risk of AML was observed. C609T odd ratio for TT genotype versus CC was obtained to be 0.91 (CI 95% = 0.51-1.63) and for CT versus CC it was 1.06 (CI 95% = 0.57-1.95). C465T odd ratio for TT genotype versus CC was calculated to be 0.22 (CI 95% = 0.009-5.56) and for CT versus CC it came out to be 3.01(CI 95% = 0.63-14.32).

  

 Conclusions

 Our findings suggest that the NQO1 C609T and C465T gene variants do not have a major influence on the susceptibility to adult AML.


Impact of FLT-3 mutations on clinical features and response to the therapy in acute promyelocytic leukemia patients
Sh. Rostami, Dr. S. Abroun, Dr. M. Noruzinia, Dr. A. Ghavamzadeh, Dr. K. Alimoghaddam,
Volume 8, Issue 4 (1-2012)
Abstract

  Abstract

 Background and Objectives

 FLT3 mutations are associated with poor outcome in acute myeloblastic leukemia(AML) patients. Only limited information is available about effects of FLT3 mutation on Acute Promyelocytic Leukemia (APL). We investigated the prevalence and impact of FLT3 mutations on the clinical characteristics and the response to treatment in APL patients treated with arsenic trioxide (As2O3).

 

 Materials and Methods

 Blood samples were collected from 115 untreated APL patients and genomic DNA was extracted by the salting-out method. FLT3-ITD and FLT3-D835 mutations were investigated by PCR-RFLP. Mann-Whitney U test and Chi-square were used for data analysis.

 

 Results

 FLT3-ITD and FLT3-D835 mutations were detected in 16 (14%) and 13(11%) of the patients, respectively. Both mutations were identified in two patients, so overall frequency of FLT3 mutations was estimated to be 23.5%. Patients positive for FLT3–ITD mutation had a higher rate of white cell counts (p= 0.005) and more frequent bcr3 type of PML/RARA fusion (p=0.04). We have not found any significant association between FLT3-D835 mutation and the clinical characteristics of patients. Between the group with FLT3 Mutations and the group without, there was no significant difference in response to therapy.

 

 Conclusions

 Complete remission induction with As2O3 may be independent of FLT3 mutation status, so As2O3 may be the first choice of APL especially in patients with FLT3 mutations. However, further studies on a large group of patients are necessary to confirm our findings.

  

 


Immunophenotyping assessment of Acute Lymphoid Leukemia in adults and its relation to induction therapy
Dr. Sh. Chavoshi, Dr. J. Eivazi Ziaei, Dr. A.a. Movasaghpour, Dr. R. Dolatkhah,
Volume 9, Issue 2 (5-2012)
Abstract

  Abstract

 Background and Objectives

  Acute Lymphoblastic Leukemia (ALL) is associated with a high rate of mortality in adults and the cure rate of the affected patients is nearly 25-40%. In order to achieve a good treatment, diagnosis of ALL subtypes and their consequent differentiation from other types of leukemia are required. The main aim of this study was to classify ALL subtypes by Flowcytometry.

 

 Materials and Methods

  One hundred and thirty four patients with ALL were recruited from Shahid Ghazi Hospital (1998 to 2006). In these studies, 86 out of 134 patients were examined by Flowcytometry.

 

 Results

 About 15.5% of the patients were considered to have pro B-cell ALL, 52% pre B-cell and mature B-cell ALL, and 32% mature T-cell ALL 64% of the patients with B-cell subtype achieved complete remission after induction therapy, while this percentage for T-cell ALL was 44%. Based on the examined markers, the differentiation of Pre T-cell ALL from mature T-cell ALL was not possible. The response to therapy was higher in the T-cell ALL group compared to B-cell.

 

 Conclusions

  In this study, the frequency of T-cell ALL was higher than the reference (32%). However, it must be mentioned that the high grade T-cell Lymphoma was differentiated from ALL. The duration of remission and survival in B-cell ALL was longer than T-cell ALL but this difference was not statistically significant.

  

 


Seroepidemiologic prevalence of HTLV in voluntary blood donors in Mashhad
Dr. H. Hatami, Dr. Gh. Karimi, Dr. H.r. Safabakhsh,
Volume 9, Issue 2 (5-2012)
Abstract

  Abstract

 Background and Objectives

  Blood transfusion is one of the routes of Human T-Lymphotropic virus (HTLV1/2) transmission. Considering that Mashhad (located in Khorasan province) is one of the areas where the virus is endemic, it seems necessary to investigate its prevalence on Mashhad blood donors.

 

 Materials and Methods

 In this descriptive study, all eligible blood donors who were anti-HTLV positive based on Elisa and confirmatory tests were considered as HTLV infected individuals and a group of healthy donors was selected as the control through 2006-2008. Data were analyzed with Chi-square by SPSS17.

 

 Results

 In this study, 250582 volunteers embarked on blood donation. Among them, 1011 (0.4 %) HTLV+ cases were confirmed. The prevalence rates of the virus were 0.47% , 0.39% and 0.35%, respectively.

 

 Conclusions

 The results of this study shows a decreasing trend in the prevalence of HTLV among blood donors. In fact blood donors are regarded as people who have less risk behaviors. To further improve blood safety, measures should be taken to identify the prevalence rate in general population and the related risk factors so that high risk donors would be excluded effectively.

 


Comparison of Cox regression and Artificial Neural Network models in prediction of survival in acute leukemia patients
S. Hosseini Teshnizi, Dr. M. Tazhibi, Dr. M. Tavasoli Farahi,
Volume 10, Issue 2 (6-2013)
Abstract

  Abstract

 Background and Objectives

 Cox regression model is one of the most common methods of survival analysis for whose application an assumption of proportional hazards needs to be established. Recently, neural network models without having certain assumptions have been shown to be suitable alternatives in predicting survival. This study aims to compare Cox regression and Artificial Neural Network ( ANN ) models to predict survival in acute leukemia patients.

  

 Materials and Methods

 In the present retrospective study, the information on 197 patients with acute leukemia in Sayyed-O-Shohada Hospital was collected using a checklist. Firstly, the assumption of proportional hazards was tested Cox regression model was fitted to the observations. To select an efficient ANN to compare with Cox regression model, the number of hidden layer neurons was changed. The prediction accuracy of the two models was compared using receiver operating characteristic (ROC) curve and kappa. Data analysis was performed using SPSS 19, Splus2000, and MatlabR 2009 software packages.

 

 Results

 Out of 9 ANN models with one hidden layer and 4 to 12 neurons, an ANN with 5 neurons in hidden layer was a superior model compared with Cox regression model. The areas under ROC curve for ANN model and Cox model were estimated to be 0.0709 and 0.458, respectively. The accuracies of prediction of survival for ANN model and Cox model were estimated as 78.9% and 50.3%, respectively.

  

 Conclusions

 Due to the high predicting accuracy of ANN models, the use of different models of ANN and their development in various fields of medical science are recommended.

  

 


Apoptotic effect of arsenic trioxide plus Azidothymidine on APL cell line (NB4) through P21 expression and cell cycle distribution changes
S. Hasani, Dr. F. Zaker, A. Zekri, A. Zaghal, Dr. K. Alimoghaddam, Dr. A. Ghavamzadeh, Dr. S.h. Ghaffari,
Volume 10, Issue 2 (6-2013)
Abstract

  Abstract

 Background and Objectives

 Arsenic trioxide (ATO) is an active drug in treatment of acute promyelocytic leukemia (APL), but has adverse effects on patients. In order to enhance antileukemic effectiveness and to reduce dosage of ATO, combinatorial effect of it with Azidothymidine (AZT) in apoptosis induction was evaluated on APL cell line (NB4).

  

 Materials and Methods

 The cells cultured and treated with 50 μM AZT and/or ATO for 48 hrs and then with apoptosis, cell cycle distribution, and P21 mRNA levels in comparison with untreated cells (control) were analyzed by flow cytometry and Real Time PCR, respectively.

 

 Results

  ATO led to induction of apoptosis (50.14% ± 7.12) in comparison with the control (3.9% ± 2.97) through the increment of the cell cycle arrest in G2/M. The apoptotic effect of ATO had been inhibited in cells treated with combination of AZT/ATO (24.35% ± 4.65). This inhibition was associated with the relative reduction of the cells in G2/M and relative increase of the cells in G1 phase. While ATO had suppressive effect on p21 gene expression (0.27±0.14), AZT (1.81 ± 0.21) and AZT/ATO (2.06 ± 0.32) induced it.

  

 Conclusions

  AZT attenuates ATO-caused apoptosis possibly through the induction of p21 expression and subsequent relative evasion from G2/M arrest and accumulation of cells in G1 phase.

  

 

 


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