更新于：2024-11-01

Chromosome 8p11 myeloproliferative syndrome

染色体8p11骨髓增殖综合征

更新于：2024-11-01

基本信息

别名

8p11 Myeloproliferative Syndrome、8p11 Stem Cell Leukemia/Lymphoma Syndrome、8p11 Stem Cell Lymphoma/Leukemia Syndrome

+ [14]

简介

Hematologic neoplasms characterized by the rearrangement of the FGFR1 gene, resulting in translocations with an 8p11 breakpoint. Patients present with a myeloproliferative neoplasm, acute myeloid leukemia, lymphoblastic lymphoma/leukemia of T or B-cell lineage, or acute leukemia of mixed phenotype.

关联

项与染色体8p11骨髓增殖综合征相关的药物

Pemigatinib

佩米替尼

靶点

FGFR1 x FGFR2 x FGFR3

作用机制

FGFR1拮抗剂 [+2]

在研机构

Incyte Biosciences Distribution BV [+6]

原研机构

Incyte Corp.

在研适应症

晚期胆管癌 [+18]

非在研适应症

晚期癌症 [+11]

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2020-04-17

RG-7112

靶点

MDM2

作用机制

MDM2抑制剂

在研机构-

原研机构

F. Hoffmann-La Roche Ltd.

在研适应症-

非在研适应症

急性淋巴细胞白血病 [+10]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与染色体8p11骨髓增殖综合征相关的临床试验

NCT05521204 / Recruiting临床2期IIT

A Study of Olverembatinib in the Treatment of Myeloid/Lymphoid Tumors With FGFR1 Rearrangement

FGFR1-rearranged myeloid/lymphoid neoplasms are a rare hematologic malignancy with very poor outcome despite intensive chemotherapy. The only curative option is thought to be allogeneic hematopoietic stem cell transplantation (HSCT) in remission.
This phase II study is aimed to evaluate the efficacy of Olverembatinib, consolidated with HSCT in the treatment of FGFR1-rearranged myeloid/lymphoid neoplasm.

开始日期2022-09-01

申办/合作机构

苏州大学附属第一医院

EUCTR2016-002596-10-GB / Unknown status临床2期

A Phase 2, Open-Label, Monotherapy, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement

开始日期2017-01-30

申办/合作机构

Incyte Corp.

DRKS00006035 / RecruitingN/A

German MPN-Registry for BCR-ABL1-Negative Myeloid Neoplasms of the German Study Group MPN (GSG-MPN) - GSG-MPN-Registry

开始日期2012-10-08

申办/合作机构-

100 项与染色体8p11骨髓增殖综合征相关的临床结果

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100 项与染色体8p11骨髓增殖综合征相关的转化医学

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0 项与染色体8p11骨髓增殖综合征相关的专利（医药）

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150

项与染色体8p11骨髓增殖综合征相关的文献（医药）

2024-05-01·American Journal of Hematology

World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management

Article

作者: Gotlib, Jason ; Shomali, William

AbstractDisease OverviewThe eosinophilias encompass a broad range of non‐hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end‐organ damage.DiagnosisHypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 109/L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, molecular testing and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.Risk StratificationDisease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2022 World Health Organization and International Consensus Classification endorse a semi‐molecular classification scheme of disease subtypes. This includes the major category “myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions” (MLN‐eo‐TK), and the MPN subtype, “chronic eosinophilic leukemia” (CEL). Lymphocyte‐variant HE is an aberrant T‐cell clone‐driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.Risk‐Adapted TherapyThe goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., <1.5 × 109/L) without symptoms or signs of organ involvement, a watch and wait approach with close follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1‐rearranged neoplasms. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant HE and HES. Hydroxyurea and interferon‐α have demonstrated efficacy as initial treatment and in steroid‐refractory cases of HES. Mepolizumab, an interleukin‐5 (IL‐5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL‐5 receptor antibody benralizumab, IL‐5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN‐eo‐TK, are under active investigation.

2024-04-01·Human Pathology

Non-sclerosing (T-cell) and sclerosing (B-cell) lymphocytic lobulitis in diagnostic breast biopsies: Clinical, imaging, and pathologic features

Article

作者: Ngo, Marie-Helene ; Lester, Susan C ; Brock, Jane E ; Yeh, Eren D ; Schulte, Stephanie ; Pinkus, Geraldine S

Lymphocytic lobulitis (LL) is characterized by prominent lymphocytic infiltrates centered on lobules. Sclerosing lymphocytic lobulitis (SCLL) associated with diabetes mellitus (DM) or autoimmune disease (AI) was the first type to be described. Subsequently, non-sclerosing LL (NSCLL) was reported as an incidental finding in prophylactic mastectomies due to high risk germline mutations or a family history of breast cancer. The two types of LL were distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter. In this study, 8 cases of NSCLL detected clinically or by screening were compared to 44 cases of SCLL. One case of NSCLL presented as a palpable mass, 2 as masses on screening, and 5 as MRI enhancement. In contrast, 80% of SCLL cases presented as palpable masses. Half the cases of NSCLL were associated with a BRCA1 or 2 mutation compared to 1 case of SCLL (2%). Three additional cases of NSCLL were associated with a strong family and/or personal history of breast cancer. Almost half (52%) of SCLL cases were associated with DM or AI, but only 25% of NSCLL. Immunoperoxidase studies confirmed a predominance of T-cells in NSCLL and B-cells in SCLL associated with DM or AI. It is important for pathologists to be aware of this new observation that NSCLL can be detected as a palpable mass or an imaging finding in diagnostic biopsies, as its presence can be indicative of a significant risk for breast cancer.

2023-09-01·International journal of hematology

Progression to B acute lymphoblastic leukemia in 8p11 myeloproliferative syndrome with t(6;8)(q27;p12).

Article

作者: Handa, Tomoyuki ; Seo, Sachiko ; Nannya, Yasuhito ; Ogawa, Seishi ; Arai, Honoka ; Iso, Hisako ; Sasaki, Ko ; Takahashi, Wataru ; Nakamura, Yuka ; Nakamura, Yuko ; Mitani, Kinuko ; Nakamura, Fumi ; Imai, Yoichi ; Ichikawa, Motoshi ; Ayabe, Rika

8p11 myeloproliferative syndrome is a rare hematological malignancy caused by the translocation of FGFR1. Patients present with a myeloproliferative neoplasm that frequently transforms into acute myeloid leukemia or T-lymphoblastic lymphoma/leukemia. Here, we report a molecular study of a patient with 8p11 myeloproliferative syndrome who developed acute B-lymphoblastic leukemia and then transformed to mixed-phenotype acute leukemia. A 67-year-old woman was diagnosed with a myeloproliferative neoplasm with t(6;8)(q27;p12) and was monitored for polycythemia vera. Four years later, she developed acute B-lymphoblastic leukemia with an additional chromosomal abnormality of - 7. Despite two induction regimens, she failed to achieve complete remission, and leukemia transformed into mixed-phenotype leukemia. Targeted sequencing of serial bone marrow samples identified the RUNX1 L144R mutation upon transformation to B-cell leukemia. After those two induction regimens, some RUNX1 mutation-positive leukemic cells obtained the JAK2 V617F mutation, which was associated with the emergence of myeloid markers, including myeloperoxidase.