Incidences of Submicroscopic Deletions Are Variable According to Disease Entities and Chromosomal Translocations in Hematologic Malignancies: Investigation by FISH.

Abstract

Submicroscopic deletions of gene in recurrent chromosomal rearrangement are known to occur frequently in hematologic malignanacies. With wide application of FISH technique in diagnosis of hematologic malignanices, it has become easy to assess the submicroscopic deletions. We investigated the incidence of submicroscopic deletion and analyzed their association with specific genetic rearrangements in various hematologic malignancies. FISH study was conducted with bone marrow cells in 336 patients with acute lymphoblastic leukemia (ALL), 223 patients with acute myeloid leukemia (AML) and 103 patients with chronic myelogenous leukemia (CML). We performed extra signal (ES)-FISH BCR/ABL, ES-FISH TEL/AML1 rearrangement and dual color split MLL rearrangement for ALL and Dual fusion-FISH (D-FISH) AML1/ETO, D-FISH PML/RARA and dual color break apart-MLL rearrangement for AML. For CML, D-FISH BCR/ABL were done. The incidence of submicroscopic deletion in the patients with chromosomal rearrangement was highest in TEL/AML1 rearrangement (65.0%), followed by BCR/ABL (10.9%), MLL (5.6%), AML1/ETO (4.0%), and PML/RARA (0.0%). Fifteen (19.0%) of 79 patients with CML showed either BCR and/or ABL deletion on derivative chromosome 9. One (5.6%) of 18 patients with MLL+ acute leukemia (5 ALL, 13 AML) showed submicroscopic deletion of telomeric portion of MLL gene. One (4.0%) of 25 patients with AML/ETO+ AML showed deletion of AML1 gene on derivative chromosome 21. None (0%) of 22 patients with PML/RARA+ AML and 59 patients with BCR/ABL+ ALL showed deletion in chromosomal rearrangement. Of note, none of 59 patients with BCR/ABL+ ALL (including major and minor rearrangement) showed submicroscopic deletion, in contrast to that of patients with BCR/ABL+ CML. In conclusion, the incidences of submicroscopic deletion was quite different among specific genetic changes and disease entities. Careful FISH study should be included in the work-up for hematologic malignancies, and their association with clinical prognosis need to be further studied.