Abstract
Mast cell leukemia (MCL) is a leukemic variant of systemic mastocytosis defined by
mast cells ≥ 20% of marrow nucleated cells. Its incidence is < 1% of all systemic
mastocytosis cases [
[1]
]. Clinical characteristics and treatment of the disease are not well established and
overall prognosis is very poor. We report a case of de novo mast cell leukemia with
novel BRAF variant, concomitant KIT exon 9 missense mutation and complex cytogenetic abnormalities. After careful review
of the literature we have not found any prior reports of concomitant BRAF and KIT
variants, and complex cytogenetic abnormalities in MCL. This case provides evidence
that MCL can have wide spectrum of genetic abnormalities as well as accumulation of
mutations in various genes including BRAF. This finding may have significant implications
for the understanding of pathogenesis, diagnosis, as well as targeted therapy of MCL.Keywords
Abbreviations:
MCL (mast cell leukemia), SM (systemic mastocytosis), FLT3 (Fms Related Receptor Tyrosine Kinase 3), IDH1 (Isocitrate Dehydrogenase (NADP (+)) 1), IDH2 (Isocitrate Dehydrogenase (NADP (+)) 2), NPM1 (Nucleophosmin 1), PPD (pack per day), GIST (gastrointestinal stromal tumor), VAF (variant allele frequency)To read this article in full you will need to make a payment
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References
Ricardo Sánchez, María Liz Paciello, Rosa M Ayala, Leyre Lorza, Teresa Cedena, M Pilar Martínez and Joaquín Martínez-López. Molecular Landscape and Clonal Evolution of Acute Mast Cell Leukemia: Case Study. 2022.
- Mast cell leukemia? Malignant mastocytosis with leukemia-like manifestations.Blood. 1957; 12: 869-882
- International working group-myeloproliferative neoplasms research and treatment (IWG-MRT) & european competence network on mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis.Blood. 2013; 121: 2393-2401
- Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427
- A case of malignant mastocytosis with circulating mast cell precursors: biologic and phenotypic characterization of the malignant clone.Leukemia. 1996; 10: 159-166
- Mast cell leukemia.Blood. 2013; 121: 1285-1295
- Efficacy and safety of midostaurin in advanced systemic mastocytosis.N Engl J Med. 2016; 374: 2530-2541
- Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage.Ann Hematol. 2015; 94: 223-231
- A scientific treatment approach for acute mast cell leukemia: using a strategy based on next-generation sequencing data.Blood Res. 2016; 51: 17-22
- Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.J Invest Dermatol. 2010; 130: 804-815
- Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line.Leukemia. 1994; 8: S18-S22
- Structure-function analyses of the kit receptor for the steel factor.Stem Cells. 1993; 11: 12-21
- Analysis of V600E BRAF and D816V KIT mutations in systemic mastocytosis.Med Oncol. 2014; 31: 123
- The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.Growth Factors. 2006; 24: 21-44
- BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study.Onco Targets Ther. 2017; 10: 965-971
- Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.Cell. 2004; 116: 855-867
- Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.Cell. 2010; 140: 209-221
- Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.Nature. 2017; 548: 234-238
- Clinical detection and categorization of uncommon and concomitant mutations involving BRAF.BMC Cancer. 2015; 24: 779
- KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors.Clin Cancer Res. 2012; 18: 1769-1776
Article Info
Publication History
Published online: June 16, 2022
Accepted:
May 16,
2022
Received in revised form:
March 22,
2022
Received:
September 16,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
