Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome.
Acute lymphoblastic leukemia (ALL) in infants generally shows distinctive biologic features and has a poor prognosis. Cytogenetic studies indicate that many infant leukemias have chromosome 11q23 translocations. Because of these findings and the distinct clinical features of infant leukemia, we investigated 30 cases of infant ALL for molecular defects of 11q23. Fourteen cases had cytogenetic abnormalities of 11q23, and all of them showed 11q23 rearrangements at the molecular level. An additional seven cases also had 11q23 molecular rearrangements, including one with normal cytogenetic analysis. Molecular abnormalities of 11q23 were significantly correlated with adverse prognostic factors, including age under 6 months, hyperleukocytosis, CD10- phenotype, and early treatment failure. Molecular analysis identified a group of infants with germline 11q23 that had a very good treatment outcome with a projected event-free survival of 80% at median follow-up of 46 months compared to 15% in infants with rearranged 11q23 (P < .001). These findings suggest that a high proportion (70%) of infants with ALL have 11q23 rearrangements and that these rearrangements are not always detectable by cytogenetic analysis. The presence of germline 11q23 DNA may identify a subgroup of infant ALL patients with a good outcome using current therapy and a different etiology for their ALL.
Chen
C S
CS
Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis.
Sorensen
P H
PH
Domer
P H
PH
Reaman
G H
GH
Korsmeyer
S J
SJ
Heerema
N A
NA
Hammond
G D
GD
Kersey
J H
JH
D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008214:Lymphocytes / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015183:Restriction Mapping; D016019:Survival Analysis; D016615:Telomere / Q000648:ultrastructure; D013997:Time Factors; D014178:Translocation, Genetic
D004247:DNA