Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia

Chapman, Jennifer R.; Geyer, Julia T.; Khanlari, Mahsa; Moul, Adrienne; Casas, Carmen; Connor, Scot T.; Fan, Yao Shan; Watts, Justin M.; Swords, Ronan; Vega, Francisco; Orazi, Attilio

doi:10.1038/modpathol.2017.148

Cited by 18 publications

(10 citation statements)

References 15 publications

(17 reference statements)

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“…Such cases are best considered as “ JAK2 mutated MPN with monocytosis” . In this regard, cases with truly overlapping features of PMF and CMML have also been well recognized . Lastly, a low JAK2 VAF may be observed in conventional cases of CMML in the absence of overt features of any MPN.…”

Section: Cmml Variantsmentioning

confidence: 99%

How I investigate chronic myelomonocytic leukemia

Sangiorgio

Arber

Orazi

2019

Int J Lab Hematology

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The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 109/L and “proliferative” CMML with WBC ≥ 13 × 109/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 109/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.

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Section: Cmml Variantsmentioning

confidence: 99%

How I investigate chronic myelomonocytic leukemia

Sangiorgio

Arber

Orazi

2019

Int J Lab Hematology

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“…These patients are suffering from both MPN and CMML or from a gray zone disease displaying hybrid features between MPN and CMML. 44,45 Our faculty concludes that it is therefore important to measure the JAK2 V617F allele burden in all patients with CMML. 39,42,43 Other drivers, such as BCR-ABL1 , are rarely found in patients with CMML.…”

Section: Introductionmentioning

confidence: 97%

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

et al. 2019

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Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diag nostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to distinguish between ‘normal’, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology.

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“…Interestingly, in three such cases, the bone marrow biopsy pictures changed after the onset of monocytosis, acquiring a marked myelomonocytic pattern with features that were more consistent with a secondary CMML than a PMF ( Figure 1 E). The occurrence of monocytosis was reported as an adverse prognostic parameter in patients with PMF or MPN in general by several groups [ 85 , 99 , 100 , 101 , 102 ], and a dose-dependent negative effect on survival has recently been re-confirmed in a large [ 85 ] study of 454 PMF patients: this study found that patients who had developed monocytosis were not only more likely to progress to leukemia (HR 2·2, 95% CI 0·99–4·9; p = 0·05), and these observations became significant for those with an absolute count >3 × 10 9 /L and who were harbouring ASXL1 mutations, although the adverse prognostic effect of monocytosis was independent of the mutational status of the driver, the ASXL1 and SRSF2 genes; no differences in the distribution of HRM mutations or of an unfavourable karyotype were registered between patients with and without monocytosis.…”

Section: Atypical/unusual Types Of Progressionmentioning

confidence: 99%

Progression in Ph-Chromosome-Negative Myeloproliferative Neoplasms: An Overview on Pathologic Issues and Molecular Determinants

Sabattini

Pizzi

Agostinelli

et al. 2021

Cancers

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Progression in Ph-chromosome-negative myeloproliferative neoplasms (MPN) develops with variable incidence and time sequence in essential thrombocythemia, polycythemia vera, and primary myelofibrosis. These diseases show different clinic-pathologic features and outcomes despite sharing deregulated JAK/STAT signaling due to mutations in either the Janus kinase 2 or myeloproliferative leukemia or CALReticulin genes, which are the primary drivers of the diseases, as well as defined diagnostic criteria and biomarkers in most cases. Progression is defined by the development or worsening of marrow fibrosis or the progressive increase in the marrow blast percentage. Progression is often related to additional genetic aberrations, although some can already be detected during the chronic phase. Detailed scoring systems for clinical usage that are mostly applied in patients with primary myelofibrosis have been defined, and the most recent ones include cytogenetic and molecular parameters with prognostic significance. Additional different clinic-pathologic changes have been reported that may occur during the course of the disease and that are, at present, classified as WHO-defined types of progression, although they likely represent such an event. The present review is meant to provide an updated overview on progression in Ph-chromosome-negative MPN, with a major focus on the pathologic side.

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Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia

Cited by 18 publications

References 15 publications

How I investigate chronic myelomonocytic leukemia

How I investigate chronic myelomonocytic leukemia

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

Progression in Ph-Chromosome-Negative Myeloproliferative Neoplasms: An Overview on Pathologic Issues and Molecular Determinants

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