Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Indian Journal of Hematology and Blood Transfusion
Published in: Indian Journal of Hematology and Blood Transfusion 1/2021

01-01-2021 | Acute Lymphoblastic Leukemia | Original Article

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

Authors: Shahid M. Baba, Arshad A. Pandith, Zafar A. Shah, Sajad A. Geelani, Mohammad Muzaffar Mir, Javid Rasool Bhat, Gul Mohammad Bhat

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 1/2021

Login to get access

Abstract

Inherited polymorphic sequence variations in drug transport genes like ABCB1 impact 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 whether ABCB1 C3435T 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 for ABCB1 polymorphisms 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. ABCB1 C3435T 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 that ABCB1 3435TT genotype increases imatinib resistance in CML and influence therapeutic outcome in B-ALL.
Literature
1.
Tsuruo T, Naito M, Tomida A et al (2003) Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci 94:15–21CrossRef
2.
Dimitris V, Volker D (2002) Challenges in treating hematologic malignancies. Semin Oncol 29:30–39CrossRef
3.
Fouad A-D, Maha A-R, Muna I et al (2008) Polymorphisms of drug-metabolizing enzymes CYP1A1, GSTT and GSTP contribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population. Leukemia Lymphoma 9:122–129
4.
Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2:48–58CrossRef
5.
Doyle LA, Yang W, Abruzzo LV et al (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670CrossRef
6.
Robey RW, Shukla S, Steadman K et al (2007) Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure. Mol Cancer Ther 6:1877–1885CrossRef
7.
Linsenmeyer ME, Jefferson S, Wolf M, Matthews JP, Board PG, Woodcock DM (1992) Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma. Br J Cancer 65:471–475CrossRef
8.
Katayama K, Noguchi K, Sugimoto Y (2014) Regulations of P-glycoprotein/ABCB1/MDR1 in human cancer cells. New J Sci 2014:476974–1–476974–10CrossRef
9.
Yasuhisa K, Shinya M, Michinori M, Kazumitsu U (2007) Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci 98:1303–1310CrossRef
10.
Aller SG, Yu J, Ward A et al (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722CrossRef
11.
Sakaeda T, Nakamura T, Okumura K (2003) Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmocodynamics of drugs. Pharmacogenomics 4:397–410CrossRef
12.
Marzolini C, Paus E, Buclin T, Kim RB (2004) Polymorphisms in human MDR1 (P glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 75:13–33CrossRef
13.
Breier A, Barancik M, Sulova Z, Uhrik B (2005) P-glycoprotein—implications of metabolism of neoplastic cells and cancer therapy. Curr Cancer Drug Targets 5:457–468CrossRef
14.
Fromm MF (2002) The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv Drug Deliv Rev 54:1295–1310CrossRef
15.
Sheng X, Zhang L, Tong N et al (2012) MDR1 C3435T polymorphism and cancer risk: a meta-analysis based on 39 case-control studies. Mol Biol Rep 39:7237–7249CrossRef
16.
Dulucq S, Bouchet S, Turcq B et al (2008) Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 112:2024–2027CrossRef
17.
Gregers J, Gréen H, Christensen IJ et al (2015) Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia. Pharmacogenomics J 15:372–379CrossRef
18.
Van Dongen JJM, Macintyre EA, Gabert JA, Delabesse E et al (1999) Standardized RT-PCR analysis of fusion gene transcripts from chromosomal aberrations in acute leukemia for detection of minimal residual disease. Leukemia 13:1910–1928
19.
Baccarani M, Deininger MW, Rosti G et al (2013) European Leukaemia Net recommendations for the management of chronic myeloid leukaemia. Blood 122:872–884CrossRef
20.
Smith M, Arthur D, Camitta B et al (1996) Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 14:18–24CrossRef
21.
Derwich K, Wachowaik J, Zajac-spychala O et al (2011) Long term results in children with standard risk acute lymphoblastic leukemia treated with 5.0 gms/m2 vs 3.0 gms/m2 methotrexate i.e according to the modified ALL BFM 90 protocol. The report of Polish pediatric leukemia/lymphoma study. Mag Eur Med oncol 4:184
22.
Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL et al (2008) Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood 111:5477–5485CrossRef
23.
Azad NA, Shah ZA, Khan MS et al (2019) No role of 3435C > T and 2677G > T ABCB1 (MDR1) gene single nucleotide polymorphisms in imatinib treatment response: a case control study on CML patients of Kashmir. Meta Gene 19:1–276CrossRef
24.
Elghannam DM, Ibrahim L, Ebrahim MA, Azmy E, Hakem H (2014) Association of MDR1 gene polymorphism (G2677T) with imatinib response in Egyptian chronic myeloid leukemia patients. Hematology 19:123–128CrossRef
25.
Sailaja K, Surekha D, Rao DN, Raghunadharao D, Vishnupriya S (2010) Association of MDR1 gene polymorphism (G2677T) with chronic myeloid leukemia. Biol Med 2:17–21
26.
Wang LH, Song YB, Zheng WL et al (2013) The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies. Cancer Cell Int 13:46–52CrossRef
27.
Pawlik A, Baskiewicz-Masiuk M, Machalinski B et al (2005) Involvement of C3435T and G2677T multidrug resistance gene polymorphisms in release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone. Eur J Pharmacol 528:27–36CrossRef
28.
Pongstaporn W, Pakakasama S, Chaksangchaichote P, Pongtheerat T, Hongeng S, Permitr S (2015) MDR1 C3435T and C1236T polymorphisms: association with high-risk childhood acute lymphoblastic leukemia. Asian Pac J Cancer Prev 16:2839–2843CrossRef
29.
Jamroziak K, Robak T (2004) Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology 9:91–105CrossRef
30.
Ni LN, Li JY, Miao KR et al (2010) Multidrug resistance gene (MDR1) polymorphisms correlate with imatinib response in chronic myeloid leukemia. Med Oncol 28:265–269CrossRef
31.
Panczyk M, Balcerczak E, Piaskowski S, Jamroziak K, Pasz- Walczak G, Mirowski M (2009) ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer. Int J Colorectal Dis 24:895–905CrossRef
32.
Tang K, Ngoi SM, Gwee PC et al (2002) Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics 12:437–450CrossRef
33.
Ghallab O, Hamed NAM, El Shafei S, Abo Elwafa R, Sherif S (2015) MDR1 gene polymorphism and outcome in Egyptian chronic myeloid leukaemia patients. J Cancer Biol Res 3:1062
34.
Skoglund K, Moreno SB, Baytar M et al (2013) ABCB1 haplotypes do not influence transport or efficacy of tyrosine kinase inhibitors in vitro. Pharmgenomics Pers Med 6:63–72PubMedPubMedCentral
35.
Au A, Aziz Baba A, Goh AS et al (2014) Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients. Biomed Pharmacother 68:343–349CrossRef
36.
Moulik NR, Parveen F, Kumar A et al (2014) Glutathione-S-transferase polymorphism and acute lymphoblastic leukemia (ALL) in north Indian children: a case-control study and meta-analysis. J Hum Genet 59:529–535CrossRef
37.
Kim DH, Sriharsha L, Xu W et al (2009) Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res 15:4750–4758CrossRef
38.
Megías-Vericat JE, Rojas L, Herrero MJ et al (2015) Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: a systematic review and meta-analysis of observational studies. Pharmacogenomics J 15(2):109–118CrossRef
39.
Rao DN, Anuradha C, Vishnupriya S et al (2010) Association of an MDR1 gene (C3435T) polymorphism with acute leukemia in India. Asian Pac J Cancer Prev 11:1063–1066PubMed
Metadata
Title
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
Authors
Shahid M. Baba
Arshad A. Pandith
Zafar A. Shah
Sajad A. Geelani
Mohammad Muzaffar Mir
Javid Rasool Bhat
Gul Mohammad Bhat
Publication date
01-01-2021
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 1/2021
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-020-01289-6

Other articles of this Issue 1/2021

Indian Journal of Hematology and Blood Transfusion 1/2021 Go to the issue

Correspondence

Orbital Rhabdomyosarcoma Infiltrating the Bone Marrow: A Potential Mimic of a Haematopoietic Neoplasm

Original Article

The Treatment Effect of Protamine on Severe Coagulopathy in Epstein–Barr Virus-Associated Hemophagocytic Lymphohistiocytosis: Case Reports and Literature Review

Original Article

Comparison of Bone Marrow Involvement with Bone Marrow Biopsy and PET–CT and Evaluation of Any Effects on Survival in Patients Diagnosed with Hodgkin and Non-Hodgkin Lymphoma

Images

Metastatic Angiosarcoma of Bone Marrow Mimicking a Pleomorphic Myeloma

Images

Loss of Normal Polyploid Spectrum as Marker of Clonality in Acute Megakaryoblastic Leukemia Evolving from Pre-Existing Primary Myelofibrosis

Original Article

A Comparative Study of Bone Marrow Squash and Wedge Aspiration Smears
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits