Marando Ludovica, Csizmar Clifford M, Patnaik Mrinal M
Division of Hematology, Department of Internal Medicine, Mayo Clinic, MN.
Haematologica. 2025 Jan 1;110(1):22-36. doi: 10.3324/haematol.2024.286061.
Chronic myelomonocytic leukemia (CMML) is an aggressive clonal stem cell disorder categorized among myelodysplastic/ myeloproliferative overlap neoplasms. While sharing features with both myelodysplastic syndromes and myeloproliferative neoplasms, 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. Age-related 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 its management. CMML is an aging-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 shortcomings 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.
慢性粒单核细胞白血病（CMML）是一种侵袭性克隆性干细胞疾病，归类于骨髓增生异常/骨髓增殖性重叠肿瘤。CMML虽然兼具骨髓增生异常综合征和骨髓增殖性肿瘤的特征，但其分子和临床特征却截然不同。CMML特异性预后模型、反应标准以及专门的临床试验的存在，凸显了其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与促炎信号之间复杂平衡的年龄相关变化，是该疾病的特征，这在其治疗中共同构成了重大的科学和临床挑战。CMML是一种与年龄相关的、临床异质性肿瘤，获批的治疗选择有限，代表了一个未满足的医疗需求领域。本综述全面分析了在精准医学不断发展的背景下，目前对驱动CMML演变的分子机制及其临床表现的理解。鉴于最新的分子发现，我们强调了现有疗法的不足，并突出了有前景的研究药物。所讨论的许多生物学发现存在于一系列急性和慢性髓系肿瘤以及克隆性造血过程中，从而拓宽了本综述的范围。
