A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms

IF 6.6 2区医学 Q1 Medicine

Cellular Oncology Pub Date : 2024-09-16 DOI:10.1007/s13402-024-00988-w

Mohammad Amjad Hussain, Shankar Prasad Das, Mithila Kulkarni, Suparna Laha

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引用次数: 0

Abstract

The c-MPL-TPO axis regulates hematopoiesis by activating various signalling cascades, including JAK/STAT, MAPK/ERK, and PIK3/AKT. Here, we have summarized how TPO is regulated by c-MPL and, how mutations in the c-MPL regulate hematopoiesis. We also focus on its non-hematological regulatory role in diseases like Unstable Angina and pathways like DNA damage repair, skeletal homeostasis, & apoptotic regulation of neurons/HSCs at the embryonic state. We discuss the therapeutic efficiency of c-MPL and, its potential to be developed as a bio-marker for detecting metastasis and development of chemo-resistance in various cancers, justifying the multifaceted nature of c-MPL. We have also highlighted the importance of c-MPL isoforms and their stoichiometry in controlling the HSC quiescent and proliferative state. The regulation of the ratio of different isoforms through gene-therapy can open future therapeutic avenues. A systematic understanding of c-MPL-isoforms would undoubtedly take one step closer to facilitating c-MPL from basic-research towards translational medicine.

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c 型骨髓增生性白血病（c-MPL）基因及其同工型的功能特点综述

c-MPL-TPO 轴通过激活各种信号级联（包括 JAK/STAT、MAPK/ERK 和 PIK3/AKT）来调节造血。在此，我们总结了 TPO 是如何受 c-MPL 调节的，以及 c-MPL 的突变是如何调节造血的。我们还关注了它在不稳定性心绞痛等疾病中的非血液学调控作用，以及 DNA 损伤修复、骨骼稳态、胚胎期神经元/造血干细胞凋亡调控等途径。我们讨论了 c-MPL 的治疗效率，以及将其开发为检测各种癌症转移和化疗耐药性发展的生物标志物的潜力，从而证明了 c-MPL 的多面性。我们还强调了 c-MPL 同工酶及其配比在控制造血干细胞静止和增殖状态中的重要性。通过基因疗法调节不同同工酶的比例，可以开辟未来的治疗途径。对 c-MPL 同工酶的系统了解无疑将为促进 c-MPL 从基础研究走向转化医学迈出坚实的一步。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.