Wilms' tumor 1 gene in hematopoietic malignancies: clinical implications and future directions
LEUKEMIA & LYMPHOMA
Authors: Luo, Ping; Jing, Wei; Yi, Kezhen; Wu, Sanyun; Zhou, Fuling
The Wilms' tumor 1 (WT1) gene is an important regulatory molecule that plays a vital role in cell growth and development. Initially, knowledge of WT1 was mostly limited to Wilms' tumor. Over the past years, numerous studies have shown that WT1 is aberrant expressed or mutated in hematopoietic malignancies, including acute leukemia (AL), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML). Currently, many studies focus on exploring the role of WT1 in hematopoietic malignancies. Such studies improve the understanding of hematopoietic malignancies, and the collection of data about WT1 expression or mutation in hematopoietic malignancies over the past years can facilitate the risk stratification of hematopoietic malignancies. In this review, we highlight the important role of WT1 in hematopoietic malignancies, discuss its potential clinical applications as a minimal residual disease (MRD) and prognostic biomarker, and evaluate the possible therapy target of WT1 in hematopoietic malignancies.
Impact of ABCB1 Gene (C3435T/A2677G) Polymorphic Sequence Variations on the Outcome of Patients with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Kashmiri Population: A Case-Control Study
INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION
Authors: Baba, Shahid M.; Pandith, Arshad A.; Shah, Zafar A.; Geelani, Sajad A.; Mir, Mohammad Muzaffar; Bhat, Javid Rasool; Bhat, Gul Mohammad
Inherited polymorphic sequence variations in drug transport genes likeABCB1impact a portion of patients with hematologic malignancies that show intrinsic or acquire resistance to treatment. Keeping in view inter-individual sensitivities for such drugs, we through this case-control study tested whetherABCB1C3435T and G2677T polymorphisms have any influence on the risk and treatment response in patients with chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Genotyping forABCB1polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism in 100 CML and 80 B-ALL patients along with 100 age and gender matched healthy controls.ABCB1C3435T and G2677T polymorphism showed no association with CML. Genotype distribution revealed significant higher frequency of TT genotype for both SNPs in B-ALL cases and associated with increased B-ALL risk (OR 2.5,p = 0.04 for 3435TT; OR 2.4,p = 0.04 for 2677TT). There was no significant difference in genotype frequency of 3435C > T and 2677G > T among resistant and responsive groups for the two leukemia types. Kaplan-Meier survival plots revealed significantly lower event free survival in CML and B-ALL patients that were carriers of 3435TT genotype (p < 0.05). Multivariate analysis considered 3435TT genotype as independent risk factor for imatinib resistance in CML cases (HR 6.24,p = 0.002) and increased relapse risk in B-ALL patients (HR 4.51,p = 0.03). The current study provides preliminary evidence of a significant association between variant TT genotype and increased B-ALL risk. Also, results suggest thatABCB13435TT genotype increases imatinib resistance in CML and influence therapeutic outcome in B-ALL.