Evidence that juvenile myelomonocytic leukemia can arise from a pluripotential stem cell

Children with neurofibromatosis type 1 (NF1) carry germline mutations in on e allele of the NF1 gene and are predisposed to myeloid malignancies, parti cularly juvenile myelomonocytic leukemia (JMML). Disruption of the remainin g NF1 allele can be found in malignant cells. Flow cytometric cell sorting techniques to isolate the malignant cell populations and molecular genetic methods to assay for somatic loss of the normal NF1 allele were used to stu dy an unusual child with NF1 and JMML who subsequently had T-cell lymphoma. The data show that malignant JMML and lymphoma cells share a common loss o f genetic material involving the normal NF1 gene and approximately 50 Mb of flanking sequence, suggesting that the abnormal T-lymphoid and myeloid pop ulations were derived from a common precursor cell. These data support the hypothesis that JMML can arise in a pluripotent hematopoietic cell. (Blood. 2000;96:2310-2313) (C) 2000 by The American Society of Hematology.