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    BIOMARKER:

    SH2B3 deletion

    i
    Other names: SH2B3, SH2B Adaptor Protein 3, Lymphocyte-Specific Adapter Protein Lnk, Signal Transduction Protein Lnk, SH2B Adapter Protein 3, LNK, Lymphocyte Adapter Protein, Lymphocyte Adaptor Protein, IDDM20
    Entrez ID:
    10019
    Related biomarkers:
    Mutation
    12ms
    Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P1, N=15, Recruiting, University of Chicago | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2023 --> Sep 2026
    Trial completion date • Trial primary completion date
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IL7R (Interleukin 7 Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 rearrangement • SH2B3 deletion
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine
    over1year
    Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P1, N=15, Recruiting, University of Chicago | Trial primary completion date: Sep 2022 --> Sep 2023
    Trial primary completion date • Combination therapy
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IL7R (Interleukin 7 Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 rearrangement • SH2B3 deletion
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine
    over1year
    AALL1521: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=171, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • EPOR (Erythropoietin Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion
    |
    cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • prednisone • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Erwinase (erwinia L-asparaginase)
    2years
    A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (AALL1521/INCB18424-269): Biologic Characteristics and Minimal Residual Disease Response of Patients with Non-CRLF2-Rearranged JAK Pathway Alterations (ASH 2022)
    Patients with Ph-like ALL harboring JAK2 or EPOR rearrangements or IL7R indels routinely had higher LDA scores and levels of EOI MRD positivity versus those with the more common CRLF2-R subtype (Tasian ASH 2020 #1095). JAK2 rearrangements occurred most frequently amongst Cohort C patients, often with previously-unknown gene partners. Although 13/23 (56.5%) of Cohort C patients were EOC MRD+, most patients demonstrated a marked decrement in EOI to EOC MRD with ruxolitinib and consolidation chemotherapy.
    Clinical • P2 data • Minimal residual disease
    |
    CRLF2 (Cytokine Receptor Like Factor 2) • PAX5 (Paired Box 5) • IL7R (Interleukin 7 Receptor) • EBF1 (EBF Transcription Factor 1) • SH2B3 (SH2B Adaptor Protein 3) • DCT (Dopachrome Tautomerase) • SSBP2 (Single Stranded DNA Binding Protein 2)
    |
    CRLF2 rearrangement • JAK2 mutation • EPOR rearrangement • JAK2 fusion • JAK2 rearrangement • SH2B3 deletion
    |
    Jakafi (ruxolitinib)
    2years
    Biallelic Deleterious Germline SH2B3 Variants Cause a Novel Clinical Syndrome of Myeloproliferation and Multi-Organ Autoimmunity (ASH 2022)
    Notably, neither of our patients had evidence of acute lymphoblastic leukemia or overt hematological malignancy and further affected individuals will need to be described in order to fully understand the breadth of the phenotype. Moreover, our data supports ruxolitinib as being a potential therapeutic option for patients with this rare novel immune dysregulatory syndrome.
    Clinical
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • CSF2 (Colony stimulating factor 2) • SH2B3 (SH2B Adaptor Protein 3) • ITGA2B (Integrin Subunit Alpha 2b)
    |
    SH2B3 deletion
    |
    Jakafi (ruxolitinib)
    over2years
    AALL1521: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=170, Recruiting, Incyte Corporation | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025
    Trial completion date • Trial primary completion date
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • EPOR (Erythropoietin Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion
    |
    cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • prednisone • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Erwinase (erwinia L-asparaginase)
    over2years
    A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=170, Recruiting, Incyte Corporation | Trial primary completion date: Feb 2024 --> Dec 2024
    Trial primary completion date
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • EPOR (Erythropoietin Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion
    |
    cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • cyclophosphamide • vincristine • prednisone • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Erwinase (erwinia L-asparaginase)
    3years
    Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia. (PubMed, Blood Adv)
    Deletion of Sh2b3 cooperates with conditional Nf1 deletion in a dose-dependent fashion. These studies illustrate that haploinsufficiency for Sh2b3 contributes to the severity of myeloproliferative disease and provide an experimental system for testing treatments for a high-risk cohort of JMML patients.
    Preclinical • Journal
    |
    NF1 (Neurofibromin 1) • SH2B3 (SH2B Adaptor Protein 3)
    |
    NF1 mutation • NF1 deletion • SH2B3 deletion
    over3years
    A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=170, Recruiting, Incyte Corporation | Trial completion date: May 2024 --> Dec 2024
    Clinical • Trial completion date
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • EPOR (Erythropoietin Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 fusion • SH2B3 deletion
    |
    cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • vincristine • prednisone • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Erwinase (erwinia L-asparaginase)
    over4years
    Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, University of Chicago | Not yet recruiting --> Active, not recruiting
    Clinical • Enrollment closed • Combination therapy
    |
    JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IL7R (Interleukin 7 Receptor) • SH2B3 (SH2B Adaptor Protein 3)
    |
    CRLF2 rearrangement • JAK2 mutation • IL7R mutation • JAK2 rearrangement • SH2B3 deletion
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • Jakafi (ruxolitinib) • vincristine • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • cyclophosphamide intravenous