Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia.
Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patients treated with interferon-alpha as first-line therapy in 3 controlled German studies with a median observation time of 7 years. Deletions were detected in pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the breakpoint. There was no significant difference in overall survival between deleted and nondeleted patients. Patients with breakpoint-spanning deletions had poorer survival compared with patients without deletions (4.7 versus 7.8 years; P = .003), but this was not significant when censored at allogeneic stem cell transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were associated with improved survival compared with cases without deletions (P = .001). Multiple Cox regression analysis indicated that deletion status (P = .007), age (P = .018), and spleen enlargement (P < .001) were significant independent indicators of survival and confirmed that only deletions spanning the ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).
Kreil
Sebastian
S
Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, United Kingdom.
Pfirrmann
Markus
M
Haferlach
Claudia
C
Waghorn
Katherine
K
Chase
Andrew
A
Hehlmann
Rüdiger
R
Reiter
Andreas
A
Hochhaus
Andreas
A
Cross
Nicholas C P
NC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics; D015996:Survival Rate
C406060:abl-bcr fusion protein, human; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr