Erythroid and megakaryocytic transformation

Abstract

Red blood cells and megakaryocytes arise from a common precursor, the megakaryocyte-erythroid progenitor and share many regulators including the transcription factors GATA-1 and GFI-1B and signaling molecules such as JAK2 and STAT5. These lineages also share the distinction of being associated with rare, but aggressive malignancies that have very poor prognoses. In this review, we will briefly summarize features of normal development of red blood cells and megakaryocytes and also highlight events that lead to their leukemic transformation. It is clear that much more work needs to be done to improve our understanding of the unique biology of these leukemias and to pave the way for novel targeted therapeutics.

Le gènePIG-A, nouveau marqueur de mutagenèse

“…Ils permettent donc la réalisation du test PIG-A sur de très petits volumes sanguins 3 . Il faut cependant noter que la fréquence spontanée des érythrocytes GPI-déficients est plus faible que celle des autres populations cellulaires 4 [4,22,23] et que l'érythrocyte étant la cellule mature de la lignée érythroïde, le temps d'expression phénotypique des mutants correspond à la durée d'une érythropoïèse, soit 18 à 20 jours chez l'homme [24]. Les réticulocytes, précurseurs immédiats des érythrocytes, constituent une autre population d'intérêt.…”

Linking anemia to inflammation and cancer: The crucial role of TNFα

“…The different mature hematopoietic cells are usually classified in lymphoid and myeloid lineages. They are regulated by distinct cytokines acting on multipotential progenitors and their committed offspring [12,13] (Fig. 1).…”

Mutational analysis of candidate tumor-associated genes in acute megakaryoblastic leukemia

“…4 However, very little is known about the etiology of adult AMKL, as no specific chromosomal rearrangements or genetic mutations have been described, apart from a rare detection of mutations in c-MPL, c-KIT, JAK2, JAK3 or FLT3. [4][5][6] Leukemia is caused through a multistep process involving genetic alterations that lead to both a proliferative advantage and a block in terminal differentiation. With respect to DS-AMKL, it is likely that trisomy 21 provides a proliferative advantage to fetal hematopoietic progenitors that harbor GATA1 mutations and that these two alterations are sufficient enough to cause TMD (transient myeloproliferative disorder), a preleukemia that is characterized by an aberrant expansion of megakaryoblasts in the fetal liver and peripheral blood.…”

“…1 With respect to the molecular basis for megakaryocytic subtypes of acute myeloid leukemia, DS-AMKL blasts uniformly harbor trisomy 21 and somatic mutations in the X-linked hematopoietic transcription factor, GATA1. 4 Distinct abnormalities, such as t(1;22)(p13;q13), which leads to expression of the OTT-MAL (RBM15-MLK1) fusion protein, t(10;11), t(9;11) or þ 8 are seen in cases of non-DS pediatric AMKL. 4 However, very little is known about the etiology of adult AMKL, as no specific chromosomal rearrangements or genetic mutations have been described, apart from a rare detection of mutations in c-MPL, c-KIT, JAK2, JAK3 or FLT3.…”

“…4 Distinct abnormalities, such as t(1;22)(p13;q13), which leads to expression of the OTT-MAL (RBM15-MLK1) fusion protein, t(10;11), t(9;11) or þ 8 are seen in cases of non-DS pediatric AMKL. 4 However, very little is known about the etiology of adult AMKL, as no specific chromosomal rearrangements or genetic mutations have been described, apart from a rare detection of mutations in c-MPL, c-KIT, JAK2, JAK3 or FLT3. [4][5][6] Leukemia is caused through a multistep process involving genetic alterations that lead to both a proliferative advantage and a block in terminal differentiation.…”