Acute Myeloid Leukemia (AML-M2) with a Novel Translocation t(5;11)(q35;q13) and Normal Expression of Cyclin D1.

Rearrangements of the long arm of chromosome 11 are commonly associated with acute leukemias, with the breakpoints clustered mainly to the 11q23 region, frequently leading to the rearrangement of the MLL gene. CCND1 (previously PRAD1, BCL1), the gene encoding cyclin D1, is located at 11q13. Overexpression of cyclin D1 represents one of the common genetic alterations in human neoplasia, leading to a change in G1-S transition and uncontrolled cell growth. Here we describe the case of a patient with acute myelogenous leukemia (AML) harboring a chromosomal translocation involving 11q13 and a new partner, chromosome 5. A 30-year-old male presented with dyspnea for one month and peripheral blood counts of: hemoglobin 4.9 g/dL, platelets 62 x 10⁹/L and leukocytes 29.5 x 10⁹/L (with 45% of blasts). Bone marrow examination showed a hypercellular marrow with 82% blasts positive for myeloperoxidase and negative for non-specific esterase. The case was classified as AML M2 according to FAB. Classical cytogenetics and spectral karyotyping (SKY) studies performed by unsynchronized culture of the marrow cells revealed an abnormal clone of 46,XY, t(5;11)(q35;q13)[20]. RT-PCR for the rearrangements MLL/AF9, MLL/AF6, MLL/AF4, MLL/ENL, and MLL/ELL were performed and were negative for all of them. Cyclin D1 overexpression was not detected in bone marrow cells by Real Time PCR. The patient was submitted to induction chemotherapy with Daunorrubicin and Cytarabine but obtained only partial remission after 2 cycles of chemotherapy (10% of blasts in bone marrow after second induction). He was than submitted to an allogeneic stem cell transplantation (SCT) from his HLA identical sister. On day +30 after SCT he was in complete hematological remission. The classical cytogenetics study after chemotherapy and bone marrow transplantation revealed karyotypes 46,XY[20] and 46,XX[15]/46,XY[15]chi, respectively. The t(5;11)(q35;q13) represents a recurrent abnormality in renal oncocytoma (benign tumors that occur predominantly in the kidney) and leads frequently to cyclin D1 overexpression. Nevertheless, this cromossomal translocation has never been described in AML.