GATA1 in normal and malignant hematopoiesis

Crispino, John D.

doi:10.1016/j.semcdb.2004.11.002

Cited by 172 publications

(158 citation statements)

References 93 publications

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“…Our results support the hypothesis that overexpression of Ik6 may contribute to the development of acute myeloid leukaemia through its ability to immortalize myeloid precursors. These data along with recent studies on the role of GATA-1s in acute megakaryoblastic leukaemia 23 highlights the newly found significance for aberrant expression of haematopoietic master gene isoforms in haematological malignancies. The development of microarrays, which allow global analysis of splice isoforms patterns, should soon allow the full extent and importance of alternative splicing for cancer to become clear.…”

Section: Discussionsupporting

confidence: 59%

The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic progenitor cells

Ruiz

Williams

Brady

2008

Intl Journal of Cancer

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Alternative pre-mRNA splicing is emerging as a major control point in both the initiation and progression of tumourigenesis. Overexpression of the dominant negative Ikaros splice isoform, Ik6, is found in many human cancers particularly leukaemias. Ik6 has been demonstrated to have a role in cell survival in both myeloid-and lymphoid cytokine-dependent cell lines. To investigate the oncogenic potential of Ik6, we retrovirally transduced murine haematopoietic progenitor cells with Ik6 and have analysed the effects on proliferation and differentiation of these precursors using myeloid and lymphoid in vitro colony formation assays. We found that Ik6 can immortalize haematopoietic progenitor cells in myeloid conditions. Using an in vivo transplantation assay, we found that Ik6 favours reconstitution by haematopoietic precursors. These findings suggest that Ik6 may play an important role in the generation of the leukaemic phenotype.

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Section: Discussionsupporting

confidence: 59%

The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic progenitor cells

Ruiz

Williams

Brady

2008

Intl Journal of Cancer

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“…3,28 TL likely arises from fetal liver hematopoietic progenitor cells after the acquisition of GATA1 mutations in the context of cellular trisomy 21. This hypothesis is supported by the detection of GATA1 mutations in DS fetal liver cells, 29 expanded numbers of megakaryocyte-erythroid progenitor cells during DS fetal hematopoiesis, 30 and the increased proliferative capacity conferred to murine fetal liver GATA1 mutations of all engrafted samples were shown to be concordant with those present in the primary human cell samples.…”

Section: Discussionmentioning

confidence: 99%

Functional differences between myeloid leukemia-initiating and transient leukemia cells in Down's syndrome

Doedens

et al. 2010

Leukemia

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Children with constitutional trisomy 21 or Down's syndrome (DS) are predisposed to develop myeloid leukemia (ML) at a young age. DS-ML is frequently preceded by transient leukemia (TL), a spontaneously resolving accumulation of blasts during the newborn period. Somatic mutations of GATA1 in the blasts of TL and DS-ML likely function as an initiating event. We hypothesized that the phenotypic difference between TL and DS-ML is due to a divergent functional repertoire of the leukemia-initiating cells. Using an NOD/SCID model, we found that cells initiating DS-ML engrafted, disseminated to distant bone marrow sites, and propagated the leukemic clone in secondary recipients. In contrast, TL cells lacked the ability to expand and to migrate, but were able to persist in the recipient bone marrow. We found some evidence of genomic progression with 1 of 9 DS-ML samples and none of 11 TL samples harboring a mutation of N-RAS. The findings of this pilot study provide evidence for the functional impact of second events underlying the transformation of TL into DS-ML and a needed experimental tool for the functional testing of these promoting events.

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“…For instance, GATA-1 is an essential transcription factor for the development of erythroid cells (39,40). GATA-2 is critical in the development of hematopoietic stem cells (41).…”

Section: Cd38mentioning

confidence: 99%

Functional Regulation of Pre-B-cell Leukemia Homeobox Interacting Protein 1 (PBXIP1/HPIP) in Erythroid Differentiation

Manavathi

Bugide

et al. 2012

Journal of Biological Chemistry

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GATA1 in normal and malignant hematopoiesis

Cited by 172 publications

References 93 publications

The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic progenitor cells

The Ikaros splice isoform, Ikaros 6, immortalizes murine haematopoietic progenitor cells

Functional differences between myeloid leukemia-initiating and transient leukemia cells in Down's syndrome

Functional Regulation of Pre-B-cell Leukemia Homeobox Interacting Protein 1 (PBXIP1/HPIP) in Erythroid Differentiation

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