Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
Division of Biostatistics and Epidemiology, Department of Healthcare Policy &Research, Weill Cornell Medical College, New York, NY, USA.
Mod Pathol. 2017 Sep;30(9):1213-1222. doi: 10.1038/modpathol.2017.45. Epub 2017 May 26.
Chronic myelomonocytic leukemia is characterized by persistent absolute monocytosis (≥1 × 10/l) in the peripheral blood and dysplasia in ≥1 lineages. In the absence of dysplasia, an acquired clonal genetic abnormality is required or causes for reactive monocytosis have to be excluded. Oligomonocytic chronic myelomonocytic leukemia showing increased monocytes but no absolute monocytosis in the peripheral blood occurs occasionally. These cases are likely classified as myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm, unclassifiable. A subset eventually develop overt chronic myelomonocytic leukemia. Better characterization of oligomonocytic chronic myelomonocytic leukemia is essential since the distinction between chronic myelomonocytic leukemia and myelodysplastic syndrome is clinically relevant. We identified 44 cases of oligomonocytic chronic myelomonocytic leukemia (≥10% peripheral blood monocytes with absolute monocyte count of 0.5-1 × 10/l) and 28 consecutive chronic myelomonocytic leukemia controls. Clinicopathologic features were compared and mutation analysis was performed. Oligomonocytic chronic myelomonocytic leukemia patients were significantly younger (median age of 65 vs 72). They had lower WBC and absolute neutrophil count, while the monocyte percentage, hemoglobin and platelet counts were similar in the two groups. The myeloid to erythroid ratio was predominantly decreased or normal, compared with the characteristic increase in chronic myelomonocytic leukemia (P=0.006). 38% of patients progressed to overt chronic myelomonocytic leukemia (median: 12 months). The overall percentage of mutations was significantly lower in oligomonocytic chronic myelomonocytic leukemia. However, the most frequent mutations in both groups were the 'signature' chronic myelomonocytic leukemia mutations in ASXL1, TET2 and SRSF2. Mutations in CBL were found exclusively in overt chronic myelomonocytic leukemia. In conclusion, we demonstrate clinical and genetic similarities between overt chronic myelomonocytic leukemia and oligomonocytic chronic myelomonocytic leukemia. The findings suggest that at least a subset of oligomonocytic chronic myelomonocytic leukemia represents early phase 'dysplastic type' chronic myelomonocytic leukemia.
慢性粒单核细胞白血病的特征是外周血中持续存在绝对单核细胞增多症（≥1×10/l）和≥1 系发育异常。在不存在发育异常的情况下，需要获得克隆遗传异常或排除反应性单核细胞增多症的原因。偶尔会出现外周血中单核细胞增多但无绝对单核细胞增多的寡单核细胞性慢性粒单核细胞白血病。这些病例可能被归类为骨髓增生异常综合征或骨髓增生异常/骨髓增殖性肿瘤，无法分类。亚组最终会发展为明显的慢性粒单核细胞白血病。更好地描述寡单核细胞性慢性粒单核细胞白血病是必要的，因为慢性粒单核细胞白血病和骨髓增生异常综合征之间的区别具有临床相关性。我们鉴定了 44 例寡单核细胞性慢性粒单核细胞白血病（外周血单核细胞≥10%，绝对单核细胞计数为 0.5-1×10/l）和 28 例连续慢性粒单核细胞白血病对照。比较了临床病理特征并进行了突变分析。寡单核细胞性慢性粒单核细胞白血病患者明显更年轻（中位年龄 65 岁 vs 72 岁）。他们的白细胞计数和绝对中性粒细胞计数较低，而两组的单核细胞百分比、血红蛋白和血小板计数相似。与慢性粒单核细胞白血病特征性增加相比，骨髓与红细胞的比值主要降低或正常（P=0.006）。38%的患者进展为明显的慢性粒单核细胞白血病（中位时间：12 个月）。寡单核细胞性慢性粒单核细胞白血病的总突变率明显较低。然而，两组最常见的突变是 ASXL1、TET2 和 SRSF2 中的“特征性”慢性粒单核细胞白血病突变。CBL 突变仅在外显型慢性粒单核细胞白血病中发现。总之，我们证明了明显的慢性粒单核细胞白血病和寡单核细胞性慢性粒单核细胞白血病之间存在临床和遗传相似性。这些发现表明，至少一部分寡单核细胞性慢性粒单核细胞白血病代表早期“发育异常型”慢性粒单核细胞白血病。
