Acute Myeloid Leukemia Research Today is a free monthly online journal that collates and summarizes the latest research about Acute Myeloid Leukemia, including details on aml, symptoms, treatment, information.

FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia.

Pollard JA, Alonzo TA, Gerbing RB, Woods WG, Lange BJ, Sweetser DA, Radich JP, Bernstein ID, Meshinchi S

Fred Hutchinson Cancer Research Center, Clinical Research Division, D2-373, 1100 Fairview Ave N, Seattle, WA 98109, USA. jpollard@fhcrc.org

Acute myeloid leukemia (AML) is a clonal disease characterized by heterogeneous involvement of hematopoietic stem cell/progenitor cell populations. Using FLT3 internal tandem duplication (FLT3/ITD) as a molecular marker, we tested the hypothesis that clinical outcome in AML correlates with disease involvement of CD34(+)/CD33(-) precursors. Diagnostic specimens from 24 children with FLT3/ITD-positive AML were sorted by fluorescence-activated cell sorting (FACS), and resultant CD34(+)/CD33(-) and CD34(+)/CD33(+) progenitors were analyzed directly and after colony-forming cell (CFC) assay for the presence of FLT3/ITD. FLT3/ITD was present in all CD34(+)/CD33(+) patient samples. In contrast, FLT3/ITD was detected in CD34(+)/CD33(-) progenitors in only 19 of 24 samples. A bipotent progenitor was affected in a subset of patients, as evidenced by the presence of FLT3/ITD in both granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) colonies. Those patients in whom CD34(+)/CD33(-) precursors harbored the FLT3/ITD had worse clinical outcome; actuarial event-free survival (EFS) at 4 years from study entry for those patients with and without FLT3/ITD detection in CD34(+)/CD33(-) progenitors was 11% +/- 14% versus 100% +/- 0%, respectively (P = .002). This study suggests that FLT3/ITD involvement in CD34(+)/CD33(-) precursors is heterogeneous and that detection of the mutation in the less-mature progenitor population may be associated with disease resistance.

Published 5 October 2006 in Blood, 108(8): 2764-9.
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