Expression of HMGA2 in PB Leukocytes and Purified CD34+ Cells from Normal Individuals and Patients with Myelofibrosis and Myeloid Metaplasia.

Background: Myelofibrosis with myeloïd metaplasia (MMM) is a rare myeloproliferative disorder which associates clonal proliferation of multipotent hematopoietic progenitors and reactive fibrosis. Deregulation and overexpression of HMGA2 has recently been demonstrated in MMM. Using quantitative RT-PCR on blood mononuclear cells from 27 patients, we found various levels of expression. It could be hypothesized that HMGA2 expression reflected the variable increase in circulating CD34+ progenitors in MMM though we failed to establish significant correlation between the level of expression and the blood enumeration of CD34+ progenitors.

Material and Methods: We studied 24 patients diagnosed as primary MMM according to the set of criteria recently updated through an Italian Consensus Conference. Six individuals free from hematologic malignancy were used as controls. We also studied-purified CD34+ cells: 8 samples were isolated from the PB of MMM patients; given the very low concentrations of progenitors in normal PB, 2 samples pooling 8 healthy donors each were also prepared. In addition, 7 CD34+ cell samples were purified from the BM of consenting subjects collected during surgery for hip replacement.

Results: We assayed HMGA2 expression in purified CD34+ populations from MMM patients and controls: both expressed HMGA2 but markedly more the CD34+ cells from the patients. We also evidenced transcripts in their CD15+ granulocytic cells suggesting that the enhanced expression of the gene affects the whole pathological clone. HMGA2, not expressed in normal blood cells, is involved in benign solid tumors of mesenchymal origin.

Conclusion: Our data support the hypothesis that its reactivation in the clonal progenitors contribute to the pathogenesis of MMM.