Indian Journal of Science and Technology

Abstract

Acute myelocytic leukemia (AML), French-American-British (FAB) classification M3 contains variable clinical disease. About 90% of the AMLM3 has specific reciprocal chromosome translocation between chromosomes15 and 17, which resulted in PML-RARα and RARα-PML chimeric genes. We analyzed 39 AMLM3 patients who showed typical clinical M3 symptoms, with simple or complex 15;17 translocation or not, by metaphase and interphase fluorescence in situ hybridization (FISH) methods using both of PML-RARα and RARα-PML chimeric probes or reverse transcriptase PCR of PML-RARα chimeric gene. Thirty-one patients reported positive for PML-RARα gene while eight patients did not. Of interest, 6 of the 31 PML-RARα positive AMLM3 patients (19.4%) did not show RARα-PML chimeric signal, which was considered to be the cases having the deletion of the region locating RARα-PML chimeric gene on der (17) chromosome either after or at the same time of formation of simple 15;17 translocation. Out of 6, 2 patients had complex 15;17 translocation of t(3;15;17) and ins(15;17). Two-way translocation model might be more acceptable to show the mechanisms for formation of complex 15;17 translocation and insertion 15;17 where insertion of a region of chromosome 17 involving RARα into PML region of chromosome 15. These precise FISH analysis also revealed that AMLM3 acquired variable chromosomal instabilities such as deletion of RARα gene and segmental jumping translocation following 15;17 translocation and the FISH analysis will be applicable for classification of AMLM3.
Keywords: 15; 17 chromosomal translocation, acute myelocytic leukemia (AML), acute promyelocytic leukemia (APL), chromosome instability, PML, RARα, FISH