Detection of c-kit point mutation Asp-816 → Val in microdissected pooled single mast cells and leukemic cells in a patient with systemic mastocytosis and concomitant chronic myelomonocytic leukemia

Sotlar, Karl; Fridrich, C; Mall, Adelheid; Jaussi, Ralf; Bültmann, B.; Valent, Peter; Horny, Hans‐Peter

doi:10.1016/s0145-2126(02)00041-3

Cited by 62 publications

(41 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Costly and time-consuming approaches such as cell sorting (30 ) and laser microdissection (31 ) have been used previously to increase the proportion of variant mast cells, but additional mast cell purification steps were not required for sensitive detection in either method described in this study. Furthermore, both methods were designed to enable detection in archival paraffin-embedded tissues.…”

Section: Discussionmentioning

confidence: 99%

Sensitive Detection of KIT D816V in Patients with Mastocytosis

et al. 2006

View full text Add to dashboard Cite

Background: The 2447 A>T pathogenic variation at codon 816 of exon 17 (D816V) in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive activation of tyrosine kinase activity and confers resistance to the tyrosine kinase inhibitor imatinib mesylate. Thus detection of this variation in SM patients is important for determining treatment strategy, but because the population of malignant cells carrying this variation is often small relative to the normal cell population, standard molecular detection methods can be unsuccessful. Methods: We developed 2 methods for detection of KIT D816V in SM patients. The first uses enriched sequencing of mutant alleles (ESMA) after BsmAI restriction enzyme digestion, and the second uses an allele-specific competitive blocker PCR (ACB-PCR) assay. We used these methods to assess 26 patients undergoing evaluation for SM, 13 of whom had SM meeting WHO classification criteria (before variation testing), and we compared the results with those obtained by direct sequencing. Results: The sensitivities of the ESMA and the ACB-PCR assays were 1% and 0.1%, respectively. According to the ACB-PCR assay results, 65% (17/26) of patients were positive for D816V. Of the 17 positive cases, only 23.5% (4/17) were detected by direct sequencing. ESMA detected 2 additional exon 17 pathogenic variations, D816Y and D816N, but detected only 12 (70.5%) of the

show abstract

Section: Discussionmentioning

confidence: 99%

Sensitive Detection of KIT D816V in Patients with Mastocytosis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Of note, there is a high correlation between KIT mutation detection and the proportion of lesional cells in the sample, as well as the sensitivity of the screening method employed [65]. Sensitivity of detection may be enhanced by enriching lesional MC by laser capture microdissection, or magnetic bead-or FACSbased cell sorting, respectively, [20,29,66] or through the use of highly sensitive PCR techniques [32]. Outside of a research setting, it is currently not standard practice to screen for KIT mutations other than those involving D816.…”

Section: Molecular Studiesmentioning

confidence: 99%

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Pardanani

2015

American J Hematol

View full text Add to dashboard Cite

Disease overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.Risk stratification: The 2008 World Health Organization classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent SM (ISM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.Management: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (+/−corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases.Investigational Drugs: Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 90:251–262, 2015. © 2015 Wiley Periodicals, Inc.

show abstract

“…Bone marrow evaluation was performed following previously established criteria for morphology, 6 histopathology, immunohistochemistry, 5,22,23 flow cytometry immunophenotyping, 11,24,25 detection of KIT mutations, 26,27 and bone marrow mast cell clonality as previously reported in detail.…”

Section: Diagnostic Work-up For Mastocytosismentioning

confidence: 99%

Evaluation of the WHO criteria for the classification of patients with mastocytosis

et al. 2011

View full text Add to dashboard Cite

Diagnosis and classification of mastocytosis is currently based on the World Health Organization (WHO) criteria. Here, we evaluate the utility of the WHO criteria for the diagnosis and classification of a large series of mastocytosis patients (n ¼ 133), and propose a new algorithm that could be routinely applied for refined diagnosis and classification of the disease. Our results confirm the utility of the WHO criteria and provide evidence for the need of additional information for (1) a more precise diagnosis of mastocytosis, (2) specific identification of new forms of the disease, (3) the differential diagnosis between cutaneous mastocytosis vs systemic mastocytosis, and (4) improved distinction between indolent systemic mastocytosis and aggressive systemic mastocytosis. Based on our results, a new algorithm is proposed for a better diagnostic definition and prognostic classification of mastocytosis, as confirmed prospectively in an independent validation series of 117 mastocytosis patients.

show abstract

Detection of c-kit point mutation Asp-816 → Val in microdissected pooled single mast cells and leukemic cells in a patient with systemic mastocytosis and concomitant chronic myelomonocytic leukemia

Cited by 62 publications

References 34 publications

Sensitive Detection of KIT D816V in Patients with Mastocytosis

Sensitive Detection of KIT D816V in Patients with Mastocytosis

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

Evaluation of the WHO criteria for the classification of patients with mastocytosis

Contact Info

Product

Resources

About