Persistence of Transcriptionally Silent BCR-ABL Rearrangements in Chronic Myeloid Leukemia Patients in Sustained Complete Cytogenetic Remission

• Published in: Leukemia & lymphoma 2001, Vol.42 (5), p.933-944
• Main Authors: Kitzis, Alain, Brizard, Françoise, Dascalescu, Christina, Chomel, Jean-Claude, Gudlhot, Francois, Brizard, André
• Format: Article
• Language: English
• Subjects: BCR-ABL rearrangement; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 9; chronic myeloid leukemia; complete cytogenetic remission; Cytogenetic Analysis; fluorescence in situ hybridization; Fusion Proteins, bcr-abl - genetics; Gene Rearrangement; Gene Silencing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; polymerase chain reaction; Translocation, Genetic
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428190109097712

Persistence of BCR-ABL rearrangements was demonstrated by D-FISH technique in chronic myeloid leukemia (CML) patients in complete cytogenetic response (CCR) after allogeneic bone marrow transplantation (BMT) or interferon-α therapy (IFN-α). Samples from bone marrow aspkate or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, fluorescent interphase in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). In all patients, FISH detected 1% to 12% nuclei with a BCR-ABL fusion gene, whereas Q-RT-PCR were negative or weakly positive. Based on these results, we hypothesize that the BCR-ABL genomic rearrangement remains unexpressed in a small percentage of cells whatever the treatment (IFN-α or BMT), and this in spite of the negativity of the RT-PCR-based classical molecular remission criterion. These data corroborate those obtained by other investigators and point to the need for follow-up of CML patients in CCR over an extensive period, at the DNA level to evaluate the residual disease and at the RNA level (Q-RT-PCR) to estimate the risk of relapse and guide the therapeutic decision. Experimental models suggesting the persistence of positive BCR-ABL cells are discussed and tentative explanations of tumor "dormancy" are proposed.