Deletion of any part of the BCR or ABL gene on the derivative chromosome 9 is a poor prognostic marker in chronic myelogenous leukemia.
To evaluate the prognostic significance of submicroscopic deletions of the ABL or BCR gene associated with t(9;22) in chronic myelogenous leukemia (CML), we investigated the incidence of an ABL or BCR deletion on derivative chromosome 9 using fluorescence in situ hybridization (FISH). FISH was performed using the LSI BCR/ABL dual-fusion translocation probe on bone marrow cells of 86 patients with CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event-free survival time (EFS) than those without ABL deletion (P = 0.020). Patients with BCR deletion showed significantly short overall survival time (OS; P = 0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed significantly short OS and EFS (median OS, 43.0 months; median EFS, 40.0 months), compared to the patients without any BCR or ABL gene deletions (median OS, 94.0 months; median EFS, 90.0 months; P = 0.041 for OS, P = 0.008 for EFS). All the patients with BCR deletion, except for one, had a concomitant ABL deletion, suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be more frequent than in patients without any deletion of the two genes (P = 0.073). Deletion of any of the BCR or ABL genes on derivative chromosome 9 was associated with both short OS and EFS. We conclude that deletion of not only the ABL gene, but also of the BCR gene, is a poor prognostic marker that indicates rapid disease progression in CML.
Lee
Young Kyung
YK
Department of Laboratory Medicine, Hallym University College of Medicine, 39 Hallymdaehak-gil, Chuncheon, 200-702, Seoul, Korea.
Kim
Young Ree
YR
Min
Hyun Chung
HC
Oh
Bo Ra
BR
Kim
Tae Young
TY
Kim
Young Soo
YS
Cho
Han Ik
HI
Kim
Hee Chan
HC
Lee
Yun Song
YS
Lee
Dong Soon
DS
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D017353:Gene Deletion; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D015994:Incidence; D007723:Korea / Q000453:epidemiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*; D015996:Survival Rate
D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr