Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-α therapy or allogeneic bone marrow transplantation

• Published in: Blood 2000-01, Vol.95 (2), p.404-409
• Main Authors: CHOMEL, J.-C, BRIZARD, F, VEINSTEIN, A, RIVET, J, SADOUN, A, KITZIS, A, GUILHOT, F, BRIZARD, A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Blotting, Southern; Bone Marrow Transplantation; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 9; Disease-Free Survival; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Gene Rearrangement; Hematologic and hematopoietic diseases; Humans; Immunosuppression; In Situ Hybridization, Fluorescence; Interferon-alpha - therapeutic use; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Time Factors; Translocation, Genetic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v95.2.404

In recent years, the prognosis of chronic myeloid leukemia (CML) has been greatly improved either with interferon-alpha (IFN-alpha) therapy or allogeneic bone marrow transplantation (BMT). In the present study, minimal residual disease was evaluated in 21 patients in complete cytogenetic response (CCR) after such treatments. Samples from bone marrow aspirates or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, interphase fluorescent 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 experiments were negative or weakly positive. Based on these results, we hypothesize that the BCR-ABL genomic rearrangement persists unexpressed in nonproliferating cells whatever the treatment (IFN-alpha or BMT). These data point to the need for follow-up of CML patients in CCR over an extensive period at the DNA level (FISH) to evaluate the residual disease and at the RNA level (Q-RT-PCR) to estimate the risk of relapse. (Blood. 2000;95:404-408)