The development of ALL, like other malignancies of hematologic origin, is believed to involve a transformation event that occurs in a single progenitor cell that has the capability for indefinite clonal expansion. The leukemogenic event may occur in committed lymphoid cells of B- or T-cell lineages or in early precursors, which gives rise to the different subtypes of ALL based on the stage of lymphoid differentiation of the cell in which the event occurred. About 80% of all cases of ALL express cell-surface markers indicative of a precursor B-cell lineage. Only 1% to 2% of cases express a phenotype typical of a mature B cell. T-cell ALL accounts for about 15% to 20% of cases and is commonly associated with features at diagnosis, such as older age, male predominance, high white blood cell (WBC) count, and extramedullary disease, all of which indicate the need for increased intensity of chemotherapy.
The identification of specific chromosomal abnormalities plays an important role in determining therapy and prognosis in certain subtypes of ALL. Some of the more common chromosomal abnormalities in ALL include the TEL-AML1 fusion gene, which by molecular techniques, can be found in 25% of cases of pre-B ALL. The presence of this translocation carries a more favorable prognosis. The bcr-abl t(9,22) p180 translocation is found in only about 3% to 5% of cases of childhood ALL. The presence of this translocation is associated with a high WBC count at diagnosis and a poor response to therapy. Rearrangements of the MLL gene at chromosome band 11q23 are found in 80% of cases of ALL in infants. Unfortunately, young children with this genetic abnormality have a very poor prognosis and a survival of less than 20% despite intensive therapy.[12,13,14,15] Children, with MLL gene rearrangements, > 1 year of age at diagnosis were found to have better prognoses than those of infants with the same translocation, but far worse than age-matched patients without rearrangements of the MLL gene.
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Cite this: Topics in Pediatric Leukemia -- Acute Lymphoblastic Leukemia - Medscape - Feb 28, 2005.