Deletion of the long arm of chromosome 7 in secondary acute nonlymphocytic leukemia and in myelodysplastic sindromes
摘要
Monosomy of chromosome (ch) 7 or partial deletion of the long arm of ch 7 is frequently observed in myelodysplastic syndromes (MDS) and secondary acute nonlymphocytic leukemia (ANLL), seen in patients with previous exposure to mutagenic agents or radiation therapy. These chromosomal abnormalities have been associated with a rapid progression of the disease and a poor response to therapy. The deletions have been described in at least three regions of ch 7 : 7q22, 7q31.1-32 and 7q36. The cell origin of MDS and ANLL could be either the CFU-GEMM stem cell or the pluripotent stem cell, but neither of these possibilities has yet been proven. The absence of the deletion in DNAs extracted by peripheral lymphocytes argues against a multipotent stem cell origin, so, we were very carefully to separate lymphocytes from myeloid cells and we refer to lymphocytes as normal cells. 147 patients whith ANLL,MDS and MPD were studied for molecular deletions of the long arm of ch 7.24 patients were secondary ANLL, 43 MDS, 30 de novo ANLL and 50 MDP mostly CML, TE, PV and MF. Peripheral blood cells from these patients were separated in lymphocytes and myeloid cells by mini macs columns and monoclonal antibodies for the myeloid antigens CD15 and CD33. After microscopical examination of the Giemsa colored smears to detect cell separation, more than 95%myelo or monocytic cells was requested to include these samples as “tumor cells”, normal cells were obtained with less restricted criteria and were mostly represented by lymphocytes. We detected the loss of heterozigosity in the long arm of ch 7 in four patients affected by secondary acute myeloid leukemia and myelodisplasia. We used PCR and Southern blotting hybridization with polymorphic DNA fragments. Monosomy of chromosome 7 has been detected in two more patients by cytogenetics. The deletions have been mapped respectively in the region 7q22 for one patient and in 7q31-32 for three more patients. In these 4 patients the deletions start in the CFU-GEMM stem cell or in a more committed stem cell as shown by the absence of the deletion in the DNAs extracted by peripheral lymphocytes. In the 2 patients with monosomy of chromosome 7 also lymphocytes and consequently a totipotent stem cell are involved.