Chronic myelomonocytic leukemia (CMML) is an aggressive clonal stem cell disorder categorized amongst myelodysplastic/myeloproliferative (MDS/MPN) overlap neoplasms. While sharing features with both MDS and MPN, CMML has distinct molecular and clinical profiles. The presence of CMML-specific prognostic models, response criteria, and dedicated clinical trials underscores a unique and complex biology. Agerelated changes affecting the bone marrow microenvironment, immune responses, and the intricate balance between epigenetic deregulation and proinflammatory signaling are characteristic of this disease, collectively posing significant scientific and clinical challenges in management. CMML is an ageing-related, clinically heterogeneous neoplasm with limited approved therapeutic options, representing an area of unmet medical need. This review offers a comprehensive analysis of the current understanding of the molecular mechanisms driving CMML evolution and its clinical manifestations within the ever-evolving landscape of precision medicine. In light of the most recent molecular discoveries, we highlight the pitfalls of existing therapies and underscore promising investigational agents. Many of the biological findings discussed are shared across a spectrum of acute and chronic myeloid neoplasms, as well as clonal hematopoiesis, broadening the scope of this review.

中文翻译：

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慢性粒单核细胞白血病：分子发病机制和治疗创新。


慢性粒单核细胞白血病 （CMML） 是一种侵袭性克隆干细胞疾病，归类为骨髓增生异常/骨髓增生性 （MDS/MPN） 重叠肿瘤。虽然 CMML 与 MDS 和 MPN 具有相同的特征，但具有不同的分子和临床特征。CMML 特异性预后模型、反应标准和专门临床试验的存在强调了独特而复杂的生物学特性。影响骨髓微环境、免疫反应以及表观遗传失调和促炎信号传导之间错综复杂的平衡的年龄相关变化是该疾病的特征，共同对管理构成重大的科学和临床挑战。CMML 是一种与衰老相关的临床异质性肿瘤，已获批的治疗选择有限，代表了未满足的医疗需求领域。本综述全面分析了目前在不断发展的精准医学领域中对驱动 CMML 进化的分子机制及其临床表现的理解。根据最新的分子发现，我们强调了现有疗法的缺陷，并强调了有前途的研究药物。讨论的许多生物学发现在一系列急性和慢性髓系肿瘤以及克隆性造血中是相同的，从而扩大了本综述的范围。