Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 24;15(1):176.
doi: 10.1038/s41408-025-01392-9.

Diagnostic relevance of SH2B3 mutations in suspected myeloid malignancies and acute leukemia: insights from a large-scale NGS-based screening study

Leïla Ben Dhia  1 , Mathieu Wemeau  2   3 , Laurène Fenwarth  1   4   5 , Alice Marceau-Renaut  1   5 , Elise Fournier  1   5 , Benoît Ducourneau  1   6 , Sabine Tricot  7 , Manon Deschildt  8 , Pascal Huchette  9 , Stéphane Darre  10 , Ilyes Benhalima  1 , Emilie Margat  11 , Claire Bories  12 , Maxime Dufossé  2   12 , Thomas Boyer  13 , Etienne Paubelle  14 , Amandine Charbonnier  14 , Delphine Lebon  14 , Julia Hieulle  2   3 , Sophie Dennetiere  3 , Zoé Malbranque  15 , Adrien Daniel  16 , Judith Bruges  17 , Laurent Pascal  18 , Jan Brijs  2 , Benjamin Carpentier  18 , Alexandre Willaume  18 , Valérie Coiteux  2 , Laure Goursaud  2 , Claude Preudhomme  1   5 , Olivier Nibourel #  1 , Nicolas Duployez #  19   20
Affiliations

Diagnostic relevance of SH2B3 mutations in suspected myeloid malignancies and acute leukemia: insights from a large-scale NGS-based screening study

Leïla Ben Dhia et al. Blood Cancer J. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: In accordance with local regulations, informed consent was obtained by the referring physicians from all patients, who were informed that their clinical and molecular data could be used for research purposes. No additional samples or analyses were performed for the purpose of this study; all data were derived from routine clinical care and were anonymized prior to analysis to ensure patient confidentiality. This study was approved by an Institutional Review Board (Number approval CSTMT359) at Lille University Hospital and conducted in accordance with the Declaration of Helsinki.

Figures

Fig. 1
Fig. 1. Landscape and classification of SH2B3 variants.
A Flowchart of the study showing selection and classification of SH2B3 variants. B Lollipop plot showing the distribution and classification of SH2B3 variants along the LNK protein structure (https://pecan.stjude.cloud/). Top panel: Tier I/II. Bottom panel: Tier III/IV. Functional domains are indicated: DD (red, aa 24-81), PH (purple, aa 194-307), and SH2 domain (blue, aa 364-462). C Frequency of SH2B3 variants by diagnostic category and tier classification in cases with clonality evidence.
Fig. 2
Fig. 2. Molecular and hematological features of patients carrying SH2B3LP variants.
A Frequency of co-mutated genes (present in >10 patients) among individuals with SH2B3LP variants (n = 236). Individuals with undetermined diagnosis were removed from the figure (n = 10). B Variant allele frequencies (VAF) of SH2B3LP variants by diagnosis (in categories with >5 patients). Horizontal bars indicate the median VAF for each disease category. C, D Forest plots showing the association between mutation status and hemoglobin concentration and platelet count. Platelet counts are log-transformed. Only genes mutated in ≥10 patients were included. Error bars represent 95% confidence intervals for the β coefficients.
See this image and copyright information in PMC

References

    1. Maslah N, Cassinat B, Verger E, Kiladjian JJ, Velazquez L. The role of LNK/SH2B3 genetic alterations in myeloproliferative neoplasms and other hematological disorders. Leukemia. 2017;31:1661–70. - PubMed
    1. Hurtado C, Erquiaga I, Aranaz P, Miguéliz I, García-Delgado M, Novo FJ, et al. LNK can also be mutated outside PH and SH2 domains in myeloproliferative neoplasms with and without V617FJAK2 mutation. Leuk Res. 2011;35:1537–9. - PubMed
    1. Zhang X, Ding Y, Li P, Bourgeois K, Rangan A, Herrick JL, et al. Null-type SH2B3 mutations are potential drivers in a subset of Ph-negative myeloproliferative neoplasms. Am J Hematol. 2024;99:1841–4. - PubMed
    1. Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Arango Ossa JE, Nannya Y, et al. Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. NEJM Evid. 2022;1:EVIDoa2200008. - PubMed
    1. Palomo L, Meggendorfer M, Hutter S, Twardziok S, Ademà V, Fuhrmann I, et al. Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms. Blood. 2020;136:1851–62. - PMC - PubMed

LinkOut - more resources