Spectra of chromosomal aberrations in 325 leukemia patients and implications for the development of new molecular detection systems

Abstract

This study investigated the spectrum of chromosomal abnormalities in 325 leukemia patients and developed optimal profiles of leukemic fusion genes for multiplex RT-PCR. We prospectively analyzed blood and bone marrow specimens of patients with acute leukemia. Twenty types of chromosomal abnormalities were detected in 42% from all patients by commercially available multiplex RT-PCR for detecting 28 fusion genes and in 35% by cytogenetic analysis including FISH analysis. The most common cytogenetic aberrations in acute myeloid leukemia patients was PML/PARA, followed by AML1/MGT8 and MLL1, and in acute lymphoid leukemia patients was BCR/ABL, followed by TEL/AML1 and MLL1 gene rearrangement. Among the negative results for multiplex RT-PCR, clinically significant t(3;3)(q21;q26.2), t(8;14)(q24;q32) and i(17)(q10) were detected by conventional cytogenetics. The spectrum and frequency of chromosomal abnormalities in our leukemia patients are differed from previous studies, and may offer optimal profiles of leukemic fusion genes for the development of new molecular detection systems.

Keywords: Chromosomal Abnormalities; Leukemia; Molecular Detection System.

Fig. 1

Representative chromosomal abnormalities. (A) Cryptic cytogenetic abnormalities were detected only in the multiplex RT-PCR system, which usually disclosed normal karyotype by conventional cytogenetic analysis. Positive band at 174base pair (arrow) in master PCR step turned out TEL/AML1 gene rearrangement by split out multiplex RT-PCR. (B) Some chromosomal abnormalities such as t(3;3) or t(8;14) should be included in multiplex RT-PCR system, which were not covered in the commercially available multiplex RT-PCR system. Arrows indicated t(3;3)(q21;q26.2). M, molecular weight marker.