KIT D816V–associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities

Marić, Irina; Robyn, Jamie; Metcalfe, Dean D.; Fay, Michael P.; Carter, Melody; Wilson, Todd M.; Fu, Weiming; Stoddard, Jennifer; Scott, Linda M.; Hartsell, Marilyn; Kirshenbaum, Arnold S.; Akin, Cem; Nutman, Thomas B.; Noël, Pierre; Klion, Amy D.

doi:10.1016/j.jaci.2007.05.024

Cited by 104 publications

(98 citation statements)

References 32 publications

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“…Investigators from the NIH and Ann Arbor could reliably partition D816V KITpositive SM-Eo from FIP1L1-PDGFRA-positive CEL into clinically distinguishable entities based on several clinical and laboratory features. 71 In the D816V KIT-positive SM-Eo cohort, gastrointestinal symptoms, urticaria pigmentosa, thrombocytosis, the median serum tryptase value and the presence of dense mast cell aggregates in the bone marrow were statistically significantly elevated or more frequently represented compared to patients with FIP1L1-PDGFRA-positive CEL. Conversely, male sex, cardiac and pulmonary symptoms, median peak absolute eosinophil count, the eosinophil to tryptase ratio and serum B12 levels were significantly elevated or more frequently represented in the FIP1L1-PDGFRA-positive CEL group.…”

Section: Role Of Fip1l1mentioning

confidence: 90%

“…A scoring system incorporating these clinical findings and laboratory tests was generated that could reliably predict the molecular status (D816V KIT versus FIP1L1-PDGFRA) of patients with peripheral eosinophilia and increased marrow mast cell burden. 71 More recently, the FIP1L1-PDGFRA fusion was also identified in five patients with AML (FAB subtypes M0, M2 and M4) and in two patients with lymphoblastic T-cell non-Hodgkin's lymphoma. 72 A search for the FIP1L1-PDGFRA rearrangement was prompted by the presence of eosinophilia either preceding or contemporaneous with the diagnosis of AML or T-NHL, or because eosinophilia persisted despite a complete hematologic remission after intensive chemotherapy.…”

Section: Role Of Fip1l1mentioning

confidence: 96%

See 1 more Smart Citation

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Gotlib¹,

2008

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Section: Role Of Fip1l1mentioning

confidence: 90%

Section: Role Of Fip1l1mentioning

confidence: 96%

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Gotlib¹,

2008

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“…Eosinophil count in excess of 1.5 3 10 9 /L was found in 1.2% of patients (4/335). However, a PB eosinophil count higher than 0.65 3 10 9 /L [21] was significantly more frequent in advanced variants such as SSM and ASM than in ISM (P < 0.001).…”

Section: Laboratory Featuresmentioning

confidence: 92%

Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients

et al. 2016

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Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n 5 255) and without (n 5 165) skin lesions, smouldering (n 5 20), aggressive (n 5 28), associated with other hematological diseases mastocytosis (n 5 21) and mast cell leukemia (n 5 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations.

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“…6 Buccal gDNA was isolated using the Gentra Puregene DNA Purification Kit (Qiagen) followed by amplification using a Qiagen REPLI-g Mini kit. HMC1, LAD2 and CD34 + derived human mast cells (NCT00001756) were cultured as described.…”

Section: Sample Processingmentioning

confidence: 99%

“…Bone marrow mast cells were analyzed as described 6 using CD45 PerCP, CD117 APC and CD25 FITC (BD Biosciences) antibodies and FACSCanto II flow cytometer (BD Biosciences).…”

Section: Immunophenotypic Analysis Of Mast Cells and Flow Cytometry Cmentioning

confidence: 99%

Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

Wilson¹,

Marić²,

Šimáková³

et al. 2010

Haematologica

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Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34 + progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. (Clinicaltrials.gov identifier: NCT00044122, NCT00001756)

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KIT D816V–associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities

Cited by 104 publications

References 32 publications

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients

Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

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