A NOVEL T(9-11)(P22-Q23) WITH ALL-1 GENE REARRANGEMENT ASSOCIATED WITH PROGRESSION OF A MYELOPROLIFERATIVE DISORDER TO ACUTE MYELOID-LEUKEMIA

We have analyzed genomic DNAs from a patient who developed acute myelo id leukemia 1 year after a myeloproliferative disorder was diagnosed. The development of the acute leukemia was associated with the acquisit ion of a t(9;11)(p22;q23) chromosome translocation. ALL-1 gene rearran gement, on chromosome 11, was present at the onset of the acute phase, but not during the chronic phase of the myeloproliferative disorder. The genomic rearrangement on chromosome 9 was within an unidentified r egion. By the use of polymerase chain reaction, we were able to determ ine that the chromosomal rearrangement was completely absent during th e chronic phase of the myeloproliferative disorder, indicating that th e ALL-1 gene rearrangement was causally related to the development of the acute phase. The rapid progression into the acute phase suggests t hat this case might be therapy related. This work provides a clear exa mple of association of a molecular defect with the development of a sp ecific clinical leukemic stage, and supports the indication that ALL-1 gene rearrangement is associated with poor clinical outcome in adult leukemias.