Search

Aim Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). Methods Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy. In addition, the human APL-derived cell line (NB4) was analyzed for the expression of survivin isoforms and capsase-3 in response to the ATO. Results Survivin and its variants were overexpressed significantly in patient's bone marrow samples compared to peripheral blood or normal samples. Their expression was decreased after ATO treatment in both NB4 cells (except survivin-2α) and APL patients along with PML-RARα copy number reduction. Downregulation of survivin isoforms was associated with an increase in both caspase-3 gene expression and its enzymatic activity levels. In a patient who did not respond to ATO treatment, expression of survivin isoforms (except survivin-2α) were highly increased during the induction therapy. Conclusion Survivin isoforms are upregulated in APL patients, and their expression is diminished during the ATO treatment. In addition, overexpression of survivin and its variants (except survivin-2α) are associated with unfavorable results, suggesting that they may play an important role in mechanisms underlying the resistance of APL cells to ATO. [ABSTRACT FROM AUTHOR]

Aim In recent years, a few cases of chronic myeloid leukemia (CML) have been reported with both BCR-ABL and JAK2V617F mutations. Moreover, mutations in the additional sex comb-like 1 ( ASXL1) gene were recently shown in various myeloid malignancies.There were no previous studies investigating the incidence of the ASXL1 and JAK2V617F mutations in Iranian patients with CML. Consequently, this study focuses on the analysis of these mutations in patients with CML. Methods In total, 66 patients with a clinical diagnosis of CML were examined at the time of diagnosis. Thirty healthy subjects were checked as controls. Exon 12 of ASXL1 was amplified from genomic DNA and bidirectionally sequenced. We also performed JAK2V617F screening by amplification refractory mutation system-polymerase chain reaction and sequencing. Results Mutations in the ASXL1 gene were found in five out of 66 CML patients (7.6%). We identified a novel variant (c.1968G > A, p.Asp656Asn) in one of the patients that has not been reported before. We also identified BCR-ABL and JAK2V617F mutations simultaneously in four patients (6%). Conclusion Our demonstration of ASXL1 mutation, a putative tumor suppressor gene, represents an important molecular abnormality in CML. We also showed that concomitant detection of BCR-ABL and JAK2V617F mutations has a relatively high incidence in Iranian patients. [ABSTRACT FROM AUTHOR]

Aim: In recent years, a few cases of chronic myeloid leukemia (CML) have been reported with both BCR-ABL and JAK2V617F mutations. Moreover, mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies.There were no previous studies investigating the incidence of the ASXL1 and JAK2V617F mutations in Iranian patients with CML. Consequently, this study focuses on the analysis of these mutations in patients with CML., Methods: In total, 66 patients with a clinical diagnosis of CML were examined at the time of diagnosis. Thirty healthy subjects were checked as controls. Exon 12 of ASXL1 was amplified from genomic DNA and bidirectionally sequenced. We also performed JAK2V617F screening by amplification refractory mutation system-polymerase chain reaction and sequencing., Results: Mutations in the ASXL1 gene were found in five out of 66 CML patients (7.6%). We identified a novel variant (c.1968G > A, p.Asp656Asn) in one of the patients that has not been reported before. We also identified BCR-ABL and JAK2V617F mutations simultaneously in four patients (6%)., Conclusion: Our demonstration of ASXL1 mutation, a putative tumor suppressor gene, represents an important molecular abnormality in CML. We also showed that concomitant detection of BCR-ABL and JAK2V617F mutations has a relatively high incidence in Iranian patients., (© 2016 John Wiley & Sons Australia, Ltd.)