Molecular and phenotypic analysis of Philadelphia chromosome-positive bilineage leukemia: possibility of a lineage switch from T-lymphoid leukemic progenitor to myeloid cells

The occurrence of acute bilineage leukemia is thought to be the malignant transformation of a myeloid or lymphoid leukemic progenitor with the potential to differentiate into the other lineages; however, the mechanisms of this lineage switch are not well understood. Here, we report on the extremely rare case of adult Philadelphia chromosome-positive acute bilineage leukemia, which is characterized by T-cell acute lymphoblastic leukemia and acute myelomonocytic leukemia. Chromosome analysis showed 46,XY,del(7)(p11.2),t(9;22)(q34;q11.2) in all metaphases and a minor BCR/ABL chimeric gene was detected in these leukemic cells by PT-PCR. When the CD5+ and CD5− cells were sorted, a fusion gene of BCR/ABL and the same clonally rearranged band of a T-cell receptor (TCR) gene were detected in both populations. Nucleotide sequencing of the TCR-γ gene revealed the clonal rearrangement of the V8-JGT2 complex in both populations. Overexpression of PU.1, which plays a fundamental role in myelomonocyte development, was found in the sorted CD34+CD7+ and CD5−, but not CD5+ cells. These results suggest that leukemic progenitor cells in the T-lineage with the del(7) and t(9;22) have the potential to differentiate into myeloid lineage, and that enforced PU.1 expression may contribute in part of this phenomenon.