更新于：2024-11-01

BCR-ABL Negative Atypical Chronic Myeloid Leukemia

BCR/ABL阴性非典型性慢性髓系白血病

更新于：2024-11-01

基本信息

别名

ACML、Atypic chron myeloid leukaemia、Atypic chron myeloid leukemia

+ [119]

简介

A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).

关联

项与 BCR/ABL阴性非典型性慢性髓系白血病相关的药物

Axatilimab-csfr

靶点

CSF-1R

作用机制

CSF-1R拮抗剂

在研机构

Syndax Pharmaceuticals, Inc. [+5]

原研机构

Incyte Corp.

在研适应症

慢性移植物抗宿主病 [+12]

非在研适应症

新型冠状病毒感染 [+5]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2024-08-14

Pacritinib

帕克替尼

靶点

ALK2 x CSF-1R x FLT3 x IRAK1 x JAK2

作用机制

ALK2抑制剂 [+4]

在研机构

Swedish Orphan Biovitrum AB [+2]

原研机构

CTI BioPharma Corp.

在研适应症

原发性骨髓纤维化 [+6]

非在研适应症

急性髓性白血病 [+16]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2022-02-28

Venetoclax

维奈克拉

靶点

Bcl-2

作用机制

Bcl-2抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2016-04-11

项与 BCR/ABL阴性非典型性慢性髓系白血病相关的临床试验

NCT06615414 / Not yet recruitingN/AIIT

Clinical and Subclinical Cardiovascular Manifestations in Philadelphia Negative Myeloproliferative Neoplasms

The primary aim of this research is to investigate the clinical and subclinical cardiovascular complications and its relationship with myeloproliferative neoplasms seeking to assess incidence, prevalence and severity in comparison to healthy group and analyze potential risk factors including genetic mutations, inflammatory markers and hematological parameters

开始日期2024-10-01

申办/合作机构

Assiut University

NCT06523556 / Recruiting临床1/2期IIT

Phase 1b/2 Study of Axatilimab (SNDX-6352) + Azacitidine (AZA) in Advanced Phase MPN, MPN/MDS Overlap or High-Risk CMML

This phase Ib/II trial tests the best dose of axatilimab and effectiveness of axatilimab with or without azacitidine for the treatment of patients with advanced phase myeloproliferative neoplasms (MPN), myeloproliferative neoplasm/myelodysplastic syndrome (MPN/MDS) overlap or high risk chronic myelomonocytic leukemia (CMML). Axatilimab is an antibody that is cloned from a single white blood cell that is known to be able to recognize cancer cells and block a protein on the surface of the white blood cells that may be involved in cancer cell growth. By blocking the proteins, this may slow or halt the growth of the cancer. Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving axatilimab with or without azacitidine may be safe and effective in treating patients with advanced phase MPN, MPN/MDS overlap or high risk CMML.

开始日期2024-08-02

申办/合作机构

Ohio State University Comprehensive Cancer Center

[+1]

NCT05993052 / RecruitingN/AIIT

Neutrophil-Lymphocyte Ratio and Carotid Plaque Burden in Patients With Philadelphia Negative Myeloproliferative Neoplasms and Their Relation to JAK2V617F Mutation

In around 90% of the patients with MPNs, an acquired mutation that promotes JAK/STAT signaling is identified [3, 4]. The JAK/STAT pathway transduces signals from cytokines including erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor.24 A point mutation that activates JAK2, JAK2V617F, is present in around 95% of patients with PV and 40% to 60% of patients with ET and MF

开始日期2022-12-15

申办/合作机构

Sohag University

100 项与 BCR/ABL阴性非典型性慢性髓系白血病相关的临床结果

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100 项与 BCR/ABL阴性非典型性慢性髓系白血病相关的转化医学

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0 项与 BCR/ABL阴性非典型性慢性髓系白血病相关的专利（医药）

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912

项与 BCR/ABL阴性非典型性慢性髓系白血病相关的文献（医药）

2024-12-31·Hematology

The characteristics of CALR mutations in myeloproliferative neoplasms: a clinical experience from a tertiary care center in Qatar and a literature review

Review

作者: Faraj, Hazem ; Ansari, Soubiya ; Akiki, Susanna Jane ; Najim, Mostafa ; Abu-Tineh, Mohammad ; Ibrahim, Mohamed Izham Mohamed ; Alateeg, Saif ; Alshurafa, Awni ; Yassin, Mohamed A

BACKGROUNDMyeloproliferative neoplasms (MPNs) are hematological disorders characterized by abnormal production of myeloid cells due to genetic mutations. Since 2013, researchers have identified somatic mutations in the Calreticulin (CALR) gene, primarily insertions or deletions, in two Philadelphia chromosome-negative MPNs; essential thrombocytosis (ET) and primary myelofibrosis (PMF), and occasionally in chronic myelomonocytic leukemia (CMML). This study aims to identify the various types of CALR mutations and their impact on CALR-positive MPN patients' clinical manifestations and outcomes.METHODSA single-center retrospective study was conducted. The data was collected from pre-existing records. The study was carried out on Philadelphia-negative MPN patients who were being followed up on at the NCCCR (National Center for Cancer Care and Research) to assess the clinical manifestation and outcome of disease treatment. All patients included, were followed in our center between January 1, 2008, and November 20, 2021.RESULTSA total of 50 patients with CALR-positive MPN were reviewed with a median follow-up of three years (1-11). This cohort included 31 (62%) patients with ET, 10 (20%) patients with PMF, and 9 (18%) patients with prefibrotic myelofibrosis (pre-MF). The study involved 38 (76%) male and 12 (24%) female patients. There were 16 (32%) patients diagnosed before the age of 40, 24 (48%) patients diagnosed between the ages of 40 and 60; and 10 (20%) patients diagnosed after the age of 60. Molecular analysis showed 24 (48%) patients with CALR type 1, 21 (42%) patients with CALR type 2, and 5 (10%) patients with none Type 1, none Type 2 CALR mutations. Two patients have double mutations; 1(2%) with none Type 1, none Type 2 CALR and JAK2 mutations, and 1(2%) with CALR type 1 and MPL mutations. The thrombotic events were 3 (6%) venous thromboembolisms, 3 (6%) abdominal veins thromboses, 2 (4%) strokes, and 4 (8%) ischemic cardiac events. Only 4 (8%) patients progressed to Myelofibrosis and were carrying CALR 1 mutations, and 1 (2%) patient progressed to AML with CALR 2 mutation.CONCLUSIONThe data shows a significant rise in CALR-positive MPN diagnoses in younger people, emphasizing the need for a better assessment tool to improve disease management and reduce complications.

2024-10-01·Leukemia

Chromosome 9p trisomy increases stem cells clonogenic potential and fosters T-cell exhaustion in JAK2-mutant myeloproliferative neoplasms

Article

作者: Bertesi, Matteo ; Tavernari, Lara ; Malerba, Marica ; Neroni, Anita ; Badii, Filippo ; Enzo, Elena ; Martinelli, Silvia ; Passamonti, Francesco ; Guglielmelli, Paola ; Potenza, Leonardo ; Carretta, Chiara ; Casarini, Livio ; Maccaferri, Monica ; Bartalucci, Niccolò ; Vannucchi, Alessandro Maria ; Pedrazzi, Francesca ; Manfredini, Rossella ; Mora, Barbara ; Luppi, Mario ; Mirabile, Margherita ; Tagliafico, Enrico ; Bianchi, Elisa ; Parenti, Sandra ; Tenedini, Elena ; Brociner, Marco ; Simoni, Manuela ; Rontauroli, Sebastiano ; Maffioli, Margherita ; Norfo, Ruggiero ; Sperduti, Samantha ; Tombari, Camilla ; Papa, Elisa ; Genovese, Elena ; Mondini, Marco

JAK2V617F is the most recurrent genetic mutation in Philadelphia-negative chronic Myeloproliferative Neoplasms (MPNs). Since the JAK2 locus is located on Chromosome 9, we hypothesized that Chromosome 9 copy number abnormalities may be a disease modifier in JAK2V617F-mutant MPN patients. In this study, we identified a subset of MPN patients with partial or complete Chromosome 9 trisomy (+9p patients), who differ from JAK2V617F-homozygous MPN patients as they carry three JAK2 alleles as well as three copies of all neighboring gene loci, including CD274, encoding immunosuppressive Programmed death-ligand 1 (PD-L1) protein. Investigation of the clonal hierarchy revealed that the JAK2V617F occurs first, followed by +9p. Functionally, CD34+ cells from +9p MPN patients demonstrated increased clonogenicity, generating a greater number of primitive colonies, due to high OCT4 and NANOG expression, with knock-down of these genes leading to a genotype-specific decrease in colony numbers. Moreover, our analysis revealed increased PD-L1 surface expression in malignant monocytes from +9p patients, while analysis of the T cell compartment unveiled elevated levels of exhausted cytotoxic T cells. Overall, here we identify a distinct novel subgroup of MPN patients, who feature a synergistic interplay between +9p and JAK2V617F that shapes immune escape characteristics and increased stemness in CD34+ cells.

2024-09-01·Annals of Hematology

Myeloproliferative neoplasms: young patients, current data and future considerations

Review

作者: Kiladjian, Jean-Jacques ; Harrison, Claire ; Ianotto, Jean-Christophe ; Sobas, Marta

The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders predominantly occurring in elderly, whereas in children and young adults are quite infrequent. Therefore, less is known about clinical presentation, genetic abnormalities, prognosis and best management strategies for this groups of patients. Currently, more cases of younger MPN patients are diagnosed. Nevertheless, diagnosis of MPNs, especially in childhood, may be difficult due to lower incidence of JAK2V617F and CALR mutations and differences in peripheral blood counts between adults and children. Challenges for younger MPN patients are longer life expectances, specific psychosocial need, fertility and pregnancy need and a long term therapy side effect (including second cancers). The most severe MPNs complication is transformation to secondary myelofibrosis (MF) or acute myeloid leukemia (AML). Optimal management of young MPNs remains a challenge as the classical risk scores fail in young MPNs. Moreover, the main objective of young MPNs therapy should be the disease outcome modification. Therefore, international collaborative work between pediatricians and "adult hematologists" is required to measure outcomes and generate protocol of management of young MPNs.