Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation.
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)
Chomel
J C
JC
Laboratoire de Génétique Cellulaire et Moléculaire (UPRES EA 2622), the Laboratoire d'Hématologie (CNRS ESA 6031), and the Département d'Hématologie et Oncologie Médicale (UPRES EA 2622), CHU de Poitiers, France.
Brizard
F
F
Veinstein
A
A
Rivet
J
J
Sadoun
A
A
Kitzis
A
A
Guilhot
F
F
Brizard
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015139:Blotting, Southern; D016026:Bone Marrow Transplantation; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007165:Immunosuppression Therapy; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000627:therapeutic use*; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl