Rearrangement between the MYH11 gene at 16p13 and D12S158 at 12p13 in a case of acute myeloid leukemia M1 (AML‐M1)

Abstract

A case of acute myeloid leukemia (AML) M1 with bone marrow eosinophilia was characterized by cytogenetics and fluorescence in situ hybridization (FISH). A complex karyotype including a der(12)t(12;17)(p12-13;q11) and a der(16)t(16;20)(p13;p11) was found at diagnosis. FISH studies with probes for chromosome 16 and for the short arm of chromosome 12 showed even more complex rearrangements. Analysis with a panel of probes for 12p showed that D12S158 spanned the breakpoint on the der(12). Unexpectedly, FISH signals were found on the der(12) and on the der(6) at band p13, the site of juxtaposition between the short arm of chromosome 16 and chromosome 20. Moreover, both YAC 854E2, containing the MYH11 gene, and cosmid ZIT133, encompassing the MYH11 breakpoint in inv(16) and t(16;16) of AML-M4 with eosinophilia, demonstrated fluorescent signals on the normal 16, on the der(16), and on the der(12). These data clearly support a reciprocal exchange between D12S158 at 12p13.3 and the MYH11 gene at 16p13. In addition, experiments with two PAC clones for the CBFB gene at 16q22 excluded the presence of a masked inv(16). An interstitial deletion, independent from the translocation and flanked by VWF and KRAS2, was also detected on the der(12).

GENETIC PROFILEOF ACUTE MYELOID LEUKEMIA

“…Until now, only one case of MYH11 involvement, independently of CBFα involvement, has been described in an AML‐M1 with bone marrow eosinophilia and a complex karyotype. A new chromosomal partner on 12p13, at locus D12S158, was found in this patient (29).…”

Characterization of 12p molecular events outside ETV6 in complex karyotypes of acute myeloid malignancies

“…Breakpoints on 12p outside ETV6 have been identified in both myeloid and lymphoid diseases (Sato et al , 1997; Le Coniat et al , 1997; Aguiar et al , 1997; Tosi et al , 1997; La Starza et al , 1998; Salomon‐Nguyen et al , 1998; Streubel et al , 1998; Andreasson et al , 1998). However, the molecular boundaries of such changes are still undetermined.…”