Co-occurring mutations in ASXL1, SRSF2, and SETBP1 define a subset of myelodysplastic/ myeloproliferative neoplasm with neutrophilia
Copyright © 2023 Elsevier Ltd. All rights reserved..
Identification of genomic signatures with consistent clinicopathological features in myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is critical for improved diagnosis, elucidation of biology, inclusion in clinical trials, and development of therapies. We describe clinical and pathological features with co-existence of mutations in ASXL1 (missense or nonsense), SRSF2, and SKI homologous region of SETBP1, in 18 patients. Median age was 68 years with a male predominance (83%). Leukocytosis and neutrophilia were common at presentation. Marrow features included hypercellularity, granulocytic hyperplasia with megakaryocytic atypia, while the majority had myeloid hyperplasia and/or erythroid hypoplasia, myeloid dysplasia, and aberrant CD7 expression on blasts. Mutations in growth signaling pathways (RAS or JAK2) were noted at diagnosis or acquired during the disease course in 83% of patients. Two patients progressed upon acquisition of FLT3-TKD (acute myeloid leukemia) or KIT (aggressive systemic mastocytosis) mutations. The prognosis is poor with only two long-term survivors, thus far, who underwent blood or marrow transplantation. We propose that the presence of co-occurring ASXL1, SRSF2, and SETBP1 mutations can be diagnostic of a subtype of MDS/MPN with neutrophilia if clinical and morphological findings align. Our report underscores the association between genotype and phenotype within MDS/MPN and that genomic signatures should guide categorization of these entities.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
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| Enthalten in: |
Leukemia research - 131(2023) vom: 01. Aug., Seite 107345 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jain, Tania [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.08.2023 Date Revised 01.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.leukres.2023.107345 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Identification of genomic signatures with consistent clinicopathological features in myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is critical for improved diagnosis, elucidation of biology, inclusion in clinical trials, and development of therapies. We describe clinical and pathological features with co-existence of mutations in ASXL1 (missense or nonsense), SRSF2, and SKI homologous region of SETBP1, in 18 patients. Median age was 68 years with a male predominance (83%). Leukocytosis and neutrophilia were common at presentation. Marrow features included hypercellularity, granulocytic hyperplasia with megakaryocytic atypia, while the majority had myeloid hyperplasia and/or erythroid hypoplasia, myeloid dysplasia, and aberrant CD7 expression on blasts. Mutations in growth signaling pathways (RAS or JAK2) were noted at diagnosis or acquired during the disease course in 83% of patients. Two patients progressed upon acquisition of FLT3-TKD (acute myeloid leukemia) or KIT (aggressive systemic mastocytosis) mutations. The prognosis is poor with only two long-term survivors, thus far, who underwent blood or marrow transplantation. We propose that the presence of co-occurring ASXL1, SRSF2, and SETBP1 mutations can be diagnostic of a subtype of MDS/MPN with neutrophilia if clinical and morphological findings align. Our report underscores the association between genotype and phenotype within MDS/MPN and that genomic signatures should guide categorization of these entities | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic myeloid malignancy | |
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| 650 | 4 | |a Myelodysplastic syndrome/myeloproliferative neoplasm | |
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| 700 | 1 | |a Ware, Alisha D |e verfasserin |4 aut | |
| 700 | 1 | |a Dalton, William Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Pasca, Sergiu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Hua-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Gocke, Christopher D |e verfasserin |4 aut | |
| 700 | 1 | |a Gondek, Lukasz P |e verfasserin |4 aut | |
| 700 | 1 | |a Xian, Rena R |e verfasserin |4 aut | |
| 700 | 1 | |a Borowitz, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Levis, Mark J |e verfasserin |4 aut | |
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