Leukemogenesis in Down Syndrome

Queiroz, Lílian Barros; Ferrari, Íris; Sá, Cezar Martins de; Mazzeu, Juliana Forte; Magalhães, Isis Quezado; Lima, Beatriz Dolabela de

doi:10.5772/24170

Cited by 1 publication

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“…In this context, based on the evidence that altered miRNA expression profiles are tumour-initiating events and a common hallmark of haematological malignancies [ 28 ], it has been hypothesized that HSA21complete or partial trisomy could promote over-expression of different miRNAs cooperating with GATA-1 S in the pathogenesis of AMKL. Interestingly, a link was found between a set of HSA21-encoded miRNAs (miR-99a, let-7c, miR-155, miR-125b-2) and leukaemogenesis [ 29 – 31 ]. Particularly, T21-dependent miR-125b-2 over-expression was found to have synergistic effects with GATA-1 S to promote proliferation and self-renewal of fetal myeloid cells.…”

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confidence: 99%

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

Sessa,

Trombetti,

Bianco

et al. 2024

Open Biol.

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Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1 S ). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1 S , we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1 S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1 S . These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1 S levels.

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Section: Introductionmentioning

confidence: 99%

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

Sessa,

Trombetti,

Bianco

et al. 2024

Open Biol.

View full text Add to dashboard Cite

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Leukemogenesis in Down Syndrome

Cited by 1 publication

References 83 publications

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

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Leukemogenesis in Down Syndrome

Cited by 1 publication

References 83 publications

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression

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miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 _S expression