Diagnosis and management of mastocytosis: an emerging challenge in applied hematology

Valent, Peter

doi:10.1182/asheducation-2015.1.98

Cited by 42 publications

(61 citation statements)

References 42 publications

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“…Major advances in the understanding of mastocytosis have been made since the 2008 classification, 19 and these are incorporated into the text of the monograph. Table 9 20 lists the 2016 categories of mastocytosis, which includes a shortening of the name of the 2008 category of "systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease (SH-AHNMD)" to the 2016 category of "systemic mastocytosis with an associated hematological neoplasm (SM-AHN)."…”

Section: Mastocytosismentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,049

7,810

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The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

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Section: Mastocytosismentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,049

7,810

View full text Add to dashboard Cite

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“…In patients with SM, neoplastic mast cells form focal and/or diffuse infiltrates in various internal organs, including the bone marrow, spleen, liver, and gastrointestinal tract . Regardless of the type of SM, the bone marrow is involved in virtually all patients .…”

Section: Introductionmentioning

confidence: 99%

“…Regardless of the type of SM, the bone marrow is involved in virtually all patients . Skin involvement is usually found in patients with ISM, while it is less frequently detected in aggressive ASM and is rarely seen in MCL …”

Section: Introductionmentioning

confidence: 99%

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A case report of systemic mastocytosis associated with multiple hematologic non–mast cell lineage diseases

Grifoni

Sciumè

Pravettoni

et al. 2019

Hematological Oncology

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Systemic mastocytosis (SM) is a hematological malignancy characterized by extracutaneous infiltration by atypical mast cells. Together with indolent SM, aggressive SM, and mast cell leukemia, the World Health Organization (WHO) recognizes another major disease subgroup: SM with an associated hematological neoplasm, which is characterized by the presence of a concurrent neoplasm, more commonly, a chronic myelomonocytic leukemia. While KIT D816V is commonly regarded as the driver mutation, the clinical presentation of SM is extremely varied. Treatment of SM might not be simple, but now more specific therapies tailored toward prognostic subgroups of patients have been developed. Here, we report a detailed description of clinical management and biological features of a systemic mastocytocis case associated with multiple hematologic non–mast cell lineage diseases.

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“…Mast cell leukemia (MCL), which is the most aggressive category of SM, is characterized by > 20% of malignant circulating MCs and has the worst prognosis of all SM categories, median overall survival being less than 6 months. Management options are limited to symptomatic treatment, and there is no curative therapy [2, 4, 5], except for allogeneic stem cell transplantation, however the majority of ASM patients are elderly and not eligible for stem cell transplant [6]. …”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis

et al. 2016

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Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC. SAHA downregulated KIT, followed by major MC apoptosis. Primary SM patient MC cultured ex vivo were even more sensitive to SAHA than HMC1.2 cells, whereas primary MC from healthy subjects were less affected. There was a correlation between cell death and SM disease severity, where cell death was more pronounced in the case of aggressive SM, with almost 100% cell death among MC from the mast cell leukemia patient. Additionally, ROSA (KIT D816V) was more affected by HDACi than ROSA (KIT WT) cells. Using ChIP qPCR, we found that the level of active chromatin mark H3K18ac/H3 decreased significantly in the KIT region. This epigenetic silencing was seen only in the KIT region and not in control genes upstream and downstream of KIT, indicating that the downregulation of KIT is exerted by specific epigenetic silencing. In conclusion, KIT D816V mutation sensitized MC to HDACi mediated killing, and SAHA may be of value as specific treatment for SM, although the specific mechanism of action requires further investigation.

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Diagnosis and management of mastocytosis: an emerging challenge in applied hematology

Cited by 42 publications

References 42 publications

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

A case report of systemic mastocytosis associated with multiple hematologic non–mast cell lineage diseases

Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis

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