Journal article
Leukemic conversion involving RAS mutations of type 1 CALR-mutated primary myelofibrosis in a patient treated for HCV cirrhosis: a case report
- Abstract:
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Somatic frameshift mutations in exon 9 of calreticulin (CALR) gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like CALR mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts. While harboring a type 1 CALR mutation, the patient underwent a leukemic transformation in less than 1 year from diagnosis, with a lethal outcome. Analysis of paired DNA samples from chronic and leukemic phases by a targeted next-generation sequencing (NGS) panel and single-nucleotide polymorphism (SNP) microarray revealed that the leukemic clone developed from the CALR-mutated clone through the acquisition of genetic events in the RAS signaling pathway: an increased variant allele frequency of the germline NRAS Y64D mutation present in the chronic phase (via an acquired uniparental disomy of chromosome 1) and gaining NRAS G12D in the blast phase. SNP microarray analysis showed five clinically significant copy number losses at regions 7q22.1, 8q11.1-q11.21, 10p12.1-p11.22, 11p14.1-p11.2, and Xp11.4, revealing a complex karyotype already in the chronic phase. We discuss how additional mutations, detected by NGS, as well as HCV infection and antiviral therapy, might have negatively impacted this type 1 CALR-mutated PMF. We suggest that larger studies are required to determine if more careful monitoring would be needed in MPN patients also carrying HCV and receiving anti-HCV treatment.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.3MB, Terms of use)
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- Publisher copy:
- 10.3389/fonc.2023.1266996
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Oncology More from this journal
- Volume:
- 13
- Article number:
- 1266996
- Publication date:
- 2023-09-29
- Acceptance date:
- 2023-09-04
- DOI:
- EISSN:
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2234-943X
- Pmid:
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37841434
- Language:
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English
- Keywords:
- Pubs id:
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1552776
- Local pid:
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pubs:1552776
- Deposit date:
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2023-10-30
Terms of use
- Copyright holder:
- Gurban et al.
- Copyright date:
- 2023
- Rights statement:
- Copyright © 2023 Gurban, Mambet, Botezatu, Necula, Neagu, Matei, Pitica, Nedeianu, Chivu-Economescu, Bleotu, Ataman, Mocanu, Saguna, Pavel, Stambouli, Sepulchre, Anton, Diaconu and Constantinescu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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