The Role of Hmga2 in the Proliferation and Expansion of a Hematopoietic Cell in Myeloproliferative Neoplasms

Abstract

: Philadelphia chromosome -negative myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by clonal proliferative hematopoiesis with increased blood cell count. Clonal expansion mechanisms in MPN and related disorders such as myelodysplastic syndromes (MDS) remain to be elucidated. Although mutations in the JAK2 gene lead to a proliferative hematopoiesis in majority of MPN and some MDS, the mutation alone does not cause a clonal expansion. In addition to JAK2 mutations, several genetic abnormalities, including TET2 and polycomb group genes involving epigenetic regulation have been reported in patients with MPN. Moreover, overexpression of HMGA2 due to removal of specific sites in its 3 untranslated region for regulatory let -7 micro RNAs may contribute to the proliferative hematopoiesis with conferring a growth advantage at the level of a hematopoietic stem cell in some cases with MPN.

HMGA2 regulates lung cancer proliferation and metastasis

“…The association between HMGA2 and cancer proliferation has been reported previously . In general, HMGA2 knockdown could inhibit cell growth in several types of cancer, which was similar to our findings in LAC.…”

“…The association between HMGA2 and cancer proliferation has been reported previously. 18,19,[31][32][33][34] In general, HMGA2 knockdown could inhibit cell growth in several types of cancer, which was similar to our findings in LAC. HMGA2 has also been shown as a direct target of ANG, a transcription factor involved in the proliferation of lung squamous carcinoma cells.…”

HMGA Proteins in Hematological Malignancies

“…While BM cells that upregulated HMGA2 have a proliferative advantage over control competitive repopulation assay in mice and BM transplant models [129], it is possible that overexpressed HMGA2 triggers a hematopoietic proliferation mechanism with a preference for platelets and inhibits the apoptosis mechanism [133,134]. All these works have raised the hypothesis that alteration of the HMGA2 protein could confer a proliferative advantage to altered progenitors, triggering the pathogenesis of MPN or other clonal hematological diseases [127], but how HMGA2 intervenes directly in the pathogenesis of MPN remains to be clarified.…”

Biology of Myeloproliferative Malignancies

“…В исследовании на трансгенных мышах избыточная экспрессия гена HMGA2 была связана с увеличением экспрессии мРНК, JAK2 и с цитокиннезависимым фосфорилированием сигнальных путей STAT3 и AKT, что вызывало пролиферацию гемопоэтических стволовых клеток. Транслокации с участием хромосом 12q13-15 приводят к усилению экспрессии HMGA2 у больных МПН, МДС и МДС/МПН [107].…”