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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation

Published on: November 26, 2018

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Differential gene expression changes and their implication on the disease progression in patients with Chronic

Ramachandran Krishna Chandran1, Narayanan Geetha2, Kunnathur Murugesan Sakthivel3

  • 1Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India.

Blood Cells, Molecules & Diseases
|April 9, 2019
PubMed

Insights

This study investigated gene expression in Chronic Myeloid Leukemia (CML). Overexpression of c-MYC, ABCB1, and BCL-2, alongside downregulation of BAD and C/EBPα/-β, drives CML progression and drug resistance.

Area of Science:

  • Molecular Biology
  • Oncology
  • Hematology

Background:

  • The molecular mechanisms driving Chronic Myeloid Leukemia (CML) progression remain incompletely understood.
  • Key functional alterations in CML include increased proliferation, reduced apoptosis, impaired differentiation, and chemoresistance.

Purpose of the Study:

  • To analyze the relative expression of genes associated with proliferation, apoptosis, differentiation, and drug resistance in various CML clinical stages.
  • To elucidate the role of specific genes in CML disease evolution and the development of Imatinib resistance.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) using SYBR Green I was employed.
  • Gene expression profiles of c-MYC, BAD, BCL-2, C/EBPα/-β, and ABCB1 were analyzed.
  • 183 CML patients (de novo CP, AP, BC, IM-resistant CP) and 30 healthy controls were studied.

Main Results:

  • Significant overexpression of c-MYC, ABCB1, and BCL-2 was detected in advanced CML phases and Imatinib-resistant CML compared to controls.
  • Downregulation of BAD and C/EBPα/-β gene expression was observed in CML patients.
  • These expression changes correlated with disease progression and drug resistance.

Conclusions:

  • A complex interplay of gene expression, including overexpression of c-MYC, ABCB1, BCL-2 and downregulation of BAD, C/EBPα/-β, is implicated in CML pathogenesis.
  • These molecular alterations contribute significantly to CML disease evolution and the emergence of drug resistance.
Keywords:
Chronic Myeloid LeukemiaDisease progressionImatinib MesylateQuantitative real time PCR

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