A t(4;11)(p12;q23) in a therapy-related acute myeloid leukemia. S.N.J. Sait¹, M.A. Claydon¹, M. Barcos², M.R. Baer³. 1) Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute, Buffalo, NY; 2) Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY; 3) Department of Medicine, Roswell Park Cancer Insitute, Buffalo, NY.
   We describe a t(4;11)(p12;q23) in a patient with therapy-related acute myeloid leukemia (t-AML) as the third reported case of t(4;11)(p12;q23) in patients with secondary leukemias. The patient is a 56-year-old female who was diagnosed in 1998 with a small lymphocytic lymphoma and treated with fludarabine and rituximab, following which she had persistent cytopenias. In 1999, she was diagnosed with multifocal invasive ductal carcinoma of the left breast, which was treated with mastectomy without adjuvant chemotherapy due to cytopenias, and in 2004 biopsy of a left chest wall mass revealed a poorly differentiated adenocarcinoma, which was treated with radiation therapy, again without chemotherapy. Bone marrow histology and karyotype were normal in 2004, but in 2005 the patient was diagnosed with acute myeloid leukemia (FAB M1), therapy-related. The karyotype at that time was 54,XX,+1,der(1;7)(q10;p10),+3,t(4;11)(p12;q23),+der(4)t(4;11)(p12;q23),+6,+6,+8,+8,+8,+19,del(20)(q11q13),+22 in all 20 cells analyzed. Fluorescence in situ hybridization (FISH) using the MLL probe (Abbott Molecular) showed rearrangement of the MLL locus and confirmed the t(4;11)(p12;q23). The t(4;11)(p12;q23) has been reported previously in two patients- one with conversion of childhood acute lymphocytic leukemia (ALL) with a t(12;21) to juvenile myelomonocytic leukemia with t(4;11) (Manor et al, 2003; Cancer Genet Cytogenet) and the other with therapy-related ALL following breast adenocarcinoma (Hayette et al, 2005; Cancer Res). Hayette et al identified the AF4p12 gene at 4p12, a human homologue of the furry gene of Drosophila, as the fusion partner of the MLL gene in their patient. It is not known whether the same gene is involved in our patient.