Molecular genetics of childhood leukemias.
OBJECTIVE
This review summarizes the molecular genetics of childhood leukemias, with emphasis on pathogenesis and clinical applications.


METHODS
We first describe the most common genetic events that occur in pediatric acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). We then illustrate how these molecular alterations may be used to alter therapy.


RESULTS
In childhood ALL, the TEL-AML1 fusion and hyperdiploidy are both associated with excellent treatment outcomes and therefore identify patients who may be candidates for less intensive therapy. In contrast, MLL gene rearrangements and the BCR-ABL fusion confer a poor prognosis; these patients may be best treated by allogeneic bone marrow transplantation in first remission.


CONCLUSIONS
Although clinical features are important prognostic indicators, genetic alterations of leukemic blasts may be better predictors of outcome for acute leukemia patients. We therefore favor risk-adapted therapy based on classification schemes that incorporate both genetic and clinical features.
Rubnitz
J E
JE
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
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D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D016044:Fusion Proteins, bcr-abl