Murine double minute X plays a central role in leukemic transformation and may be a promising target for leukemia prevention strategies

Ueda, Koki

doi:10.1016/j.exphem.2023.04.001

Cited by 1 publication

(1 citation statement)

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“…Also, we reported a novel p53-independent function of MDMX that activates WNT/β-catenin signaling via a reduced abundance of β-catenin degrader CK1α 111) . For the details of p53 dependent and independent functions of MDMX and its role in hematopoiesis, please refer to our newest review 112) . In this review, we focus on the role of MDMX in myeloid malignancies.…”

Section: The Role Of Mdmx In Myeloid Malignanciesmentioning

confidence: 99%

Cellular carcinogenesis in preleukemic conditions:drivers and defenses

Ueda,

Ikeda

2024

FJMS

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Acute myeloid leukemia (AML) arises from preleukemic conditions. We have investigated the pathogenesis of typical preleukemia, myeloproliferative neoplasms, and clonal hematopoiesis. Hematopoietic stem cells in both preleukemic conditions harbor recurrent driver mutations ; additional mutation provokes further malignant transformation, leading to AML onset. Although genetic alterations are defined as the main cause of malignant transformation, nongenetic factors are also involved in disease progression. In this review, we focus on a nonhistone chromatin protein, high mobility group AT -hook2 (HMGA2), and a physiological p53 inhibitor, murine double minute X (MDMX). HMGA2 is mainly overexpressed by dysregulation of microRNAs or mutations in polycomb components, and provokes expansion of preleukemic clones through stem cell signature disruption. MDMX is overexpressed by altered splicing balance in myeloid malignancies. MDMX induces leukemic transformation from preleukemia via suppression of p53 and p53 -independent activation of WNT/βcatenin signaling. We also discuss how these nongenetic factors can be targeted for leukemia prevention therapy.

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Section: The Role Of Mdmx In Myeloid Malignanciesmentioning

confidence: 99%