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Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated
C S Chen1, P H Sorensen, P H Domer
1Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis.
Insights
Infant acute lymphoblastic leukemia (ALL) often involves 11q23 rearrangements, detectable by molecular analysis. Germline 11q23 DNA indicates a favorable prognosis, unlike rearranged 11q23, which correlates with poor outcomes.
Area of Science:
- Pediatric Oncology
- Molecular Genetics
- Hematologic Malignancies
Background:
- Infant acute lymphoblastic leukemia (ALL) presents unique biologic features and a poor prognosis.
- Cytogenetic studies suggest frequent chromosome 11q23 translocations in infant leukemias.
Purpose of the Study:
- To investigate molecular defects of 11q23 in 30 infant ALL cases.
- To correlate 11q23 molecular abnormalities with clinical and prognostic factors.
- To assess the prognostic significance of germline versus rearranged 11q23 DNA.
Main Methods:
- Molecular analysis of 11q23 in 30 infant ALL samples.
- Correlation of molecular findings with cytogenetics, clinical features, and treatment outcomes.
- Survival analysis comparing patients with germline versus rearranged 11q23.
Main Results:
- Seventy percent of infant ALL cases showed 11q23 molecular rearrangements, with 14 cases also having cytogenetic abnormalities.
- 11q23 molecular abnormalities correlated with adverse prognostic factors: younger age, hyperleukocytosis, CD10- phenotype, and early treatment failure.
- Infants with germline 11q23 had significantly better event-free survival (80%) compared to those with rearranged 11q23 (15%).
Conclusions:
- A high proportion of infant ALL cases harbor 11q23 rearrangements, not always detected by cytogenetics.
- Molecular analysis of 11q23 is crucial for identifying infants with ALL.
- Germline 11q23 DNA identifies a subgroup of infant ALL patients with a favorable prognosis, suggesting a distinct etiology.
Abstract:
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.