RAPID COMMUNICATION All Patients With the T(11; 16)(q23; p13.3) That Involves MLL and CBP Have Treatment-Related Hematologic Disorders

The involvement of 11q23-balanced translocations in acute some variability in the breakpoint because it was on the leukemia after treatment with drugs that inhibit the function der(16) in three patients, on the der(11) in another, and split of DNA topoisomerase II (topo II) is being recognized with in four others. We assume that the critical fusion gene is increasing frequency. We and others have shown that the 5*MLL/3*CBP. Our series of patients is unusual because three gene at 11q23 that is involved in all of these treatmentof them presented with a myelodysplastic syndrome (MDS) related leukemias is MLL (also called ALL1, Htrx, and HRX). most similar to chronic myelomonocytic leukemia (CMMoL) In general, the translocations in these leukemias are the and one other had dyserythropoiesis; MDS is rarely seen in same as those occurring in de novo leukemia [eg, t(9;11), 11q23 translocations either de novo or with t-AML. Using t(11;19), and t(4;11)], with the treatment-related leukemias FISH and these same probes to analyze the lineage of bone accounting for no more than 5% to 10% of any particular marrow cells from one patient with CMMoL, we showed translocation type. We have cloned the t(11;16)(q23;p13.3) that all the mature monocytes contained the fusion genes and have shown that it involves MLL and CBP (CREB binding as did some of the granulocytes and erythroblasts; none of protein). The CBP gene was recently identified as a partner the lymphocytes contained the fusion gene. The function of gene in the t(8;16) that occurs in acute myelomonocytic leuMLL is not well understood, but many domains could target kemia (AML-M4) de novo and rarely in treatment-related the MLL protein to particular chromatin complexes. CBP is acute myeloid leukemia. We have studied eight t(11;16) paan adapter protein that is involved in regulating transcriptients, all of whom had prior therapy with drugs targetting tion. It is also involved in histone acetylation, which is topo II with fluorescence in situ hybridization (FISH) using thought to contribute to an increased level of gene expresa probe for MLL and a cosmid contig covering the CBP gene. sion. The fusion gene could alter the CBP protein such that Both probes were split in all eight patients and the two it is constitutively active; alternatively, it could modify the derivative (der) chromosomes were each labeled with both chromatin-association functions of MLL. probes. Use of an approximately 100-kb PAC located at the q 1997 by The American Society of Hematology. breakpoint of chromosome 16 from one patient revealed