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Biology and treatment of infant leukemias
Insights
Infant leukemias, especially those with MLL gene rearrangements, have a poor prognosis. Understanding their biology is key to developing better treatments for these rare childhood cancers.
Area of Science:
- Pediatric Hematology Oncology
- Cancer Genetics
- Molecular Biology
Background:
- Leukemias of infancy comprise lymphoid and myeloid subtypes, representing a small percentage of childhood acute leukemias.
- MLL gene rearrangements on chromosome 11q23 are the most frequent genetic abnormalities in infant ALL and AML.
- Infant leukemias, particularly those with MLL rearrangements, are associated with specific clinical features and a poor prognosis.
Purpose of the Study:
- To summarize the current understanding of infant leukemias, including their subtypes, genetic abnormalities, clinical presentations, and outcomes.
- To highlight the significant role of MLL gene rearrangements in infant leukemias.
- To identify the challenges and future directions in treating infant leukemias, especially MLL-rearranged cases.
Main Methods:
- Review of existing literature on infant leukemias.
- Analysis of genetic abnormalities, focusing on MLL/11q23 rearrangements.
- Correlation of clinical features with specific leukemia subtypes and genetic profiles.
- Comparison of outcomes for different infant leukemia classifications.
Main Results:
- Infant leukemias have distinct characteristics, with MLL rearrangements being highly prevalent (70-80% in ALL, ~60% in AML).
- Infants with MLL-rearranged ALL present with hyperleukocytosis, organomegaly, CNS involvement, and a poor prognosis.
- Infant AML and congenital leukemia forms, especially with MLL involvement, carry a dismal outlook, necessitating differentiation from transient myeloproliferative disorders.
Conclusions:
- Significant progress has been made in understanding the biology of infant leukemias.
- Effective treatment development, particularly for MLL-rearranged leukemias, remains a critical challenge.
- Distinguishing congenital leukemia from transient myeloproliferative disorders is crucial for appropriate management.
Abstract:
The leukemias of infancy, characterized by an equal distribution of lymphoid and myeloid subtypes, account for 2.5-5% of the acute lymphoblastic leukemias (ALL) and 6-14% of the acute myeloid leukemias (AML) of childhood. Rearrangements of the MLL gene on chromosome 11q23 are the most common genetic abnormalities in both ALL and AML, occurring in 70-80% and approximately 60% of cases, respectively. Infants with ALL and a rearrangement of MLL typically present with hyperleukocytosis, massive organomegaly, CNS involvement, CD10- B-lineage phenotype and myeloid-associated antigen (CD15) expression. Prognosis in these cases is uniformly poor, whereas in similar cases without the genetic defect, it is good to intermediate. The presenting features of infant AML include monoblastic or myelomonoblastic morphology, hyperleukocytosis and extramedullary involvement. Expected outcome approximates that for ALL (approximately 30% long-term survival rate). Rare congenital forms of lymphoid or myeloid leukemia, manifested at birth or during the first month of life, carry a dismal prognosis, especially when a MLL/11q23 rearrangement is present; such cases should be carefully distinguished by chromosomal/molecular analysis and cell culture techniques from transient myeloproliferative disorders which require only supportive care but close follow-up for subsequent development of leukemia. Juvenile chronic myeloid leukemia also can occur in infants and may be responsive to chemotherapy alone. Rapid progress has been made over the past decade in understanding the biology of infant leukemias. The biggest challenge now is to develop more effective treatment, especially for patients with MLL rearrangements.