Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases

Reham A Rashed,Dalia Y Kadry,Nahed Abd El Wahab,Maha El Taweel,Thoreya Abd El Hameed

doi:10.7314/apjcp.2015.16.17.7875

Abstract

The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p- value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value= <0.001, 0.045, 0.041, <0.008 and 0.025 respectively). Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.

Highlights

Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous disease characterized by clonal proliferation of myeloid precursors and maturation arrest, with accumulation of acquired genetic alterations in hematopoietic progenitor cells that disturb normal mechanisms of cell growth, proliferation and differentiation (Dohner 2005)
Fifty de novo adult acute myeloid leukemia patients and ten healthy age and sex matched controls were included in this study who presented to the National Cancer Institute, in the period between February 2010 and March 2012
We did not detect BAALC and erythroblast transformation-specific related gene (ERG) m-RNA transcripts, by real time reverse - transcription - polymerase chain reaction (RT-PCR), in normal bone marrow cells obtained from 10 healthy controls

Summary

Introduction

Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous disease characterized by clonal proliferation of myeloid precursors and maturation arrest, with accumulation of acquired genetic alterations in hematopoietic progenitor cells that disturb normal mechanisms of cell growth, proliferation and differentiation (Dohner 2005). The resulting molecular alterations disrupt almost every facet of cell transformation These processes include the inappropriate proliferation in the absence of normal growth signals, indefinite self-renewal in a manner analogous to a stem cell, escape from programmed cell death, inhibition of differentiation, aberrant cell cycle checkpoint control, genomic instability and multi-organ dissemination of leukemic cells (Lichtman and Sternberg, 2005). There was a statistically significant correlation between BAALC and ERG gene expression and age (p- value =0.004 and 0.019, respectively). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value=

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