SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML
Rebecca R. LabordeMrinal M. PatnaikTerra L. LashoChristy FinkeCurtis A. HansonRyan A. KnudsonRhett P. KetterlingAnimesh PardananiAyalew Tefferi
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SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMMLKeywords:
Chronic myelomonocytic leukemia
Hematology
Chronic myelomonocytic leukemia
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Monocytosis
Chronic myelomonocytic leukemia
Osteosclerosis
Leukocytosis
Myeloproliferative neoplasm
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A subset of patients with chronic myelomonocytic leukemia (CMML) presents with significance myelofibrosis. In myelodysplastic syndromes, significant myelofibrosis has been associated with adverse outcomes and p53 dysregulation. However, in CMML the clinical and molecular correlates of significant myelofibrosis at presentation remain poorly understood. From a cohort of 651 CMML patients, we identified retrospectively 20 (3.1%) cases with moderate to severe reticulin fibrosis (CMML-F) detected at diagnosis, and we compared them to CMML patients without fibrosis (n=631) seen during the same period. Patients with CMML-F had a median age of 69.8 years (range, 24.8 to 91.2 y) and most (13; 65%) were men. Patients with CMML-F differed significantly from other CMML patients across the following parameters: white blood count, absolute monocyte count, serum lactate dehydrogenase level, splenomegaly, and bone marrow blast percentage. Notably, the frequency of JAK2 p.V617F mutation was higher in CMML-F patients compared with other CMML patients (P<0.001). Most CMML-F patients (12/20; 60%) had myeloproliferative CMML. Dysregulation of p53 was uncommon in CMML-F. CMML-F patients tended to have a shorter median overall survival compared with other CMML patients (P=0.079). Multivariate analysis using the Cox proportional hazards model showed an independent association between CMML-F and overall survival (P=0.047). In summary, unlike typical CMML, CMML-F is commonly associated with JAK2 p.V617F. The high frequency of myeloproliferative features and JAK2 p.V617F mutation, and the low frequency of p53 dysregulation, suggest that fibrosis in the context of CMML has a different pathogenesis from that previously reported in myelodysplastic syndrome.
Chronic myelomonocytic leukemia
White blood cell
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The authors declare no conflict of interest.
Acute megakaryoblastic leukemia
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Myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders which generally occur in older adults but may also affect children. Primary MDS should be distinguished from secondary MDS associated with antineoplastic or immunosuppressive therapy (t-MDS), exposure to toxic compounds, or genetic disorders [1]. Chronic myelomonocytic leukemia (CMML) has been considered a variant of MDS [1] and fibrotic forms have been observed in up to 16% of cases [2]. Accordingly, the histologic evaluation of a trephine bone marrow biopsy is of critical importance for the evaluation of fibrotic or hypocellular MDS since these patterns are not reflected by the cytological examination.
Ruxolitinib
Chronic myelomonocytic leukemia
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SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML
Chronic myelomonocytic leukemia
Hematology
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Chronic myelomonocytic leukemia
Myeloproliferative Disorders
Primary (astronomy)
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Introduction: Leukemia is a hematological disorder which needs timely diagnosis and early treatment because at initially leukemic cell burden is low. So, the chances of achieving complete remission will be highest. Aims: The present study was undertaken for correlation of patient’s signs and symptoms with their laboratory findings like CBC, peripheral smear findings, immunophenotyping to know the lineage specificity and cytogenetics to know molecular abnormality. Methods and Material: The blood samples of suspected patients were received and examined at Hematology and Surgical pathology sections of Central Diagnostic Laboratory from November 2018 to June 2020. The clinical history was obtained, CBC was performed, peripheral smear and bone marrow samples were received for morphological examination and special investigations like Immunophenotyping, Cytogenetics and fish. Results: Out of the 110 cases, 17 were ALL, 33 were AML, 16 were CLL, 29 were CML. other 15 cases were distributed in acute leukemia, lymphoma, myelofibrosis and acute undifferentiated leukemia. Conclusions: Present study revealed that acute leukemia was more prevalent than chronic leukemia. The most common type of leukemia was AML followed by CML, ALL and CLL. ALL was mostly observed in children whereas CML and CLL were mostly observed in adults. AML mostly observed in adults.
Immunophenotyping
Hematology
Bone marrow examination
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Chronic myelomonocytic leukemia
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Patients with a myeloproliferative neoplasm (MPN) sometimes show a chronic myelomonocytic leukemia (CMML)-like phenotype but, according to the 2016 WHO classification, a documented history of an MPN excludes the diagnosis of CMML. Forty-one patients with an MPN (35 polycythemia vera (PV), 5 primary myelofibrosis, 1 essential thrombocythemia) and a CMML-like phenotype (MPN/CMML) were comprehensively characterized regarding clinical, hematologic, biologic and molecular features. The white blood cell counts in MPN/CMML patients were not different from CMML patients and PV patients. The hemoglobin values and platelet counts of these patients were higher than in CMML but lower than in PV, respectively. MPN/CMML patients showed myelomonocytic skewing, a typical in vitro feature of CMML but not of PV. The mutational landscape of MPN/CMML was not different from JAK2-mutated CMML. In two MPN/CMML patients, development of a CMML-like phenotype was associated with a decrease in the JAK2 V617F allelic burden. Finally, the prognosis of MPN/CMML (median overall survival (OS) 27 months) was more similar to CMML (JAK2-mutated, 28 months; JAK2-nonmutated 29 months) than to PV (186 months). In conclusion, we show that patients with MPN and a CMML-like phenotype share more characteristics with CMML than with PV, which may be relevant for their classification and clinical management.
Chronic myelomonocytic leukemia
Myeloproliferative neoplasm
Leukocytosis
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