Conversion of childhood acute lymphocytic leukemia (L2) with a double t(12;21) to juvenile myelomonocytic leukemia with a novel t(4;11)(p12;q23): a cytogenetic, morphologic, and immunophenotypic study.

Here we describe a cytogenetic and flow-cytometric study of a case in which a conversion of childhood acute lymphocytic leukemia (ALL) into juvenile myelomonocytic leukemia (JMML) occurred. A 3-year-old boy diagnosed CALLA+, pre-B-ALL with double t(12;21) (by fluorescence in situ hybridization analysis), was treated as per the BFM protocol. A cytogenetic analysis performed at 17 months into treatment showed no t(12;21) in bone marrow (BM) cells; however, a novel translocation, namely, t(4;11), involving the p12 locus on chromosome 4 and the MLL gene at 11q23 was detected in monocytes. No cytogenetic abnormalities were found either in Epstein-Barr virus-transformed B cells or in phytohemagglutinin-stimulated T-lymphoid cells. Flow-cytometric analysis demonstrated an asynchronous expression of the antigenic determinants in populations of granulocytic and monocytoid cells: 60% of monocytes expressed low levels of CD14, an unusually high level of CD15, and no CD13 or HLA-DR antigens; 74% of myeloid cells expressed no CD13. Our results indicate that the transformation from B-cell ALL to JMML in this case occurred most probably in the granulocyte-erythroid-macrophage-megakaryocyte progenitor cells without involving the lymphoid cell line. To date, the child is 10 months off therapy and asymptomatic, with t(4;11) in only 3% of the cells.