Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Abstract

Deletions on chromosomes 5 and 7 are frequently seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is assumed that these deletions indicate loss of tumor suppressor genes on these chromosomes and until these tumor suppressor genes are identified, the functional consequences of these deletions and the molecular basis of these myeloid disorders cannot be completely understood. We evaluated loss of heterozygosity (LOH) in 44 patients (18 MDS and 26 AML, diagnosed according to WHO classification criteria) at diagnosis, using a four-microsatellite marker panel: an intragenic marker on the 7th intron of gene IRF-1 of the 5q31.1 region and three markers located inside the 7q31.1 region and correlated the LOH with karyotype abnormalities. The microsatellites chosen corresponded to chromosome regions frequently deleted in MDS/ AML. The samples with Q (peak area) less than or equal to 0.50 were indicative of LOH. The percent of informative samples (i.e., heterozygous) for the intragenic microsatellite in gene IRF-1 and in loci D7S486, D7S515 and D7S522 were 66.6, 73.7, 75.5, and 48.8%, respectively. Cytogenetic abnormalities by G-banding were found in 36% (16/44) of the patients (2 of 18 MDS and 14 of 26 AML patients). We found a significantly positive association of the occurrence of LOH with abnormal karyotype (P < 0.05; chisquare test) and there were cases with LOH but the karyotype was normal (by G-banding). These data indicate that LOH in different microsatellite markers is possibly an event previous to chromosomal abnormalities in these myeloid neoplasias.

Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

“…Meanwhile, there were some differences between the chromosome abnormalities (+8, -8, -20, 20q-, -Y, -7, 5q-) in this study and those of previous studies ( 18 - 20 , 33 ). Among them, the deletion of chromosome 8 (-8) was not found in the studies by Blau et al ( 20 , 33 ) and Pinheiro et al ( 34 ), but it was identified in the studies by Flores-Figueroa et al ( 12 , 19 ) and our study. These inconsistent results may be attributed to the different detection methods (Song et al ( 18 ), Flores-Figueroa et al ( 12 , 19 ), and Pinheiro et al ( 34 ): trypsine-giemsa banding) or to the different populations (Flores-Figueroa et al ( 12 , 19 ): Mexico; Blau et al ( 20 , 33 ): Germany; Pinheiro et al ( 34 ): Brazil).…”