The Mutational Landscape in Polycythemia Vera: Phenotype, Genotype, and Prognostic Correlates.

Polycythemia vera (PV) is invariably associated with a JAK2 mutation, with over 50% of patients harboring additional non-JAK2 mutations. In the current study, 319 patients with PV underwent NGS at diagnosis or in chronic phase PV (Group A: N = 270, 85%) or at the time of fibrotic (Group B; N = 37, 12%) or leukemic (Group C; N = 12, 4%) transformation. Mutational frequencies involving TP53/SRSF2/IDH1/U2AF1 were significantly (p < 0.

Multihit TP53 Mutations in Myeloproliferative Neoplasms and Acute Myeloid Leukemia: Comparative Analysis of Survival and Risk Factors in 142 Informative Cases.

A total of 142 patients with myeloproliferative neoplasms (MPNs) or acute myeloid leukemia (AML) associated with multihit TP53 mutations (mTP53 ) were accessed from the Mayo Clinic database and included (i) chronic phase MPN (MPN-CP; N = 19), (ii) accelerated phase MPN (MPN-AP; N = 14), (iii) blast phase MPN (MPN-BP; N = 28), and (iv) AML (N = 81). Concurrent ASXL1 , EZH2 , IDH1, and IDH2 were more common in MPN-BP-mTP53 compared to AML-mTP53 . At median of 11.

De novo isolated myeloid sarcoma: comparative analysis of survival in 19 consecutive cases.

Institutional database search (1999-2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67).

Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome.

CWP232291 (CWP291) is a small-molecule inhibitor of Wnt signaling that causes degradation of β-catenin via apoptosis induction through endoplasmic reticulum stress activation. This first-in-human, open-label, dose-escalation study to evaluate the safety, maximum tolerated dose (MTD), and preliminary efficacy of CWP291 enrolled 69 patients with hematologic malignancies (acute myeloid leukemia [AML], n = 64; myelodysplastic syndrome, n = 5) in 15 dose-escalation cohorts of 4 to 334 mg/m2 using a modified 3+3 design and 1 dose-expansion cohort. CWP291 was administered IV daily for 7 days every 21 days.

Development of a prognostically relevant cachexia index in primary myelofibrosis using serum albumin and cholesterol levels.

Serum albumin and cholesterol levels predict survival in primary myelofibrosis, independent of each other and contemporary risk models. The cachexia index, determined by serum albumin and cholesterol levels, might further refine current prognostic models in myelofibrosis.

Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial.

Background: Symptomatic burden from constitutional symptoms, anemia, and splenomegaly-related symptoms are common and morbidity inducing in patients with myelofibrosis (MF). The authors previously developed a MF-specific instrument for capturing the burden of MF-associated disease-related symptoms, the Myelofibrosis Symptom Assessment Form.

Methods: The authors evaluated the usefulness of serial administration of the Myelofibrosis Symptom Assessment Form as an instrument for the assessment of symptomatic burden and improvement in conjunction with the therapeutic clinical trial of the open label phase 2 trial of the JAK1 and JAK2 inhibitor INCB018424 in patients with MF.

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.

Background: Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor.

International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis.

Among 200 patients with primary myelofibrosis, karyotype at diagnosis was abnormal in 83 (42%). To assess their individual prognostic impact, specific cytogenetic abnormalities with more than or equal to 5 informative cases were identified and the rest grouped separately as "other abnormalities." Median survival in patients with sole +9 (n = 6), sole 20q- (n = 21), sole 13q- (n = 8), normal karyotype (n = 117), "other abnormalities" (n = 28), complex karyotype (n = 13), and sole +8 (n = 7) were "not reached," 112, 105, 80, 46, 34, and 28 months, respectively (P = .

The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis.

Quality of life (QoL) in patients with myelofibrosis (MF) is severely compromised by severe constitutional symptoms (i.e. fatigue, night sweats, fever, weight loss), pruritus, and symptoms from frequently massive hepatosplenomegaly.

Validation of a new three-color fluorescence in situ hybridization (FISH) method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations.

The PDGRFA locus has become a gene of interest based on mutational activation in various myeloid neoplasms and the availability of targeted therapies (i.e., imatinib mesylate) to its overexpression.

MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients.

Chronic basophilic leukemia: a distinct clinico-pathologic entity?

Objective: We sought to better define a group of rare and poorly understood myeloproliferative disorders that are characterized by prominent chronic basophilia in the absence of the Philadelphia chromosome (Ph) or its molecular equivalent.

Methods: We screened our institution's electronic database from 1975 onwards, and identified four such cases. Clinical data and bone marrow pathology were carefully reviewed for these patients.