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Gene Symbol CBL
Synonyms C-CBL | CBL2 | FRA11B | NSLL | RNF55
Gene Description CBL, Cbl proto-oncogene, is an E3 ubiquitin-protein ligase involved in cell signaling and ubiquitination of tyrosine kinases (PMID: 23085373). CBL mutations, often resulting in a loss of function, have been identified primarily in myeloid neoplasms, including myelodysplastic syndrome, acute myeloid leukemia, chronic myeloid leukemia, myelofibrosis, and juvenile myelomonocytic leukemia (PMID: 25477533).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CBL Y371H FLT3 wild-type hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Y371H FLT3 wild-type hematologic cancer sensitive Midostaurin Preclinical Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture, reduced leukemia burden and prolonged survival in animal models (PMID: 31309543). 31309543
CBL Y371H FLT3 wild-type hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Y371H FLT3 wild-type hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Y371H FLT3 wild-type hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Y371H FLT3 wild-type hematologic cancer decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). 31309543
CBL Y371H FLT3 pos hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell line xenograft Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Y371H (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive Midostaurin + PRT062607 Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive PRT062607 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Nexavar (sorafenib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Y371H FLT3 pos hematologic cancer sensitive PRT062607 + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Vanflyta (quizartinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell line xenograft Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Q365_E366insSK (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Midostaurin + PRT062607 Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive PRT062607 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Nexavar (sorafenib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive PRT062607 + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Vanflyta (quizartinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Crenolanib + PRT062607 Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Crenolanib resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Gilteritinib + PRT062607 Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Xospata (gilteritinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Entospletinib + Midostaurin Preclinical - Cell culture Actionable In a preclinical study, the addition of Entospletinib to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). 31943762
CBL mutant bone marrow cancer sensitive Quizartinib Preclinical Actionable In a preclinical study, Vanflyta (quizartinib) reduced white blood cell counts and decreased myeloid cell invasion in a CBL mutant mouse model with myeloproliferative disorder (PMID: 22990016). 22990016
CBL mutant systemic mastocytosis not applicable N/A Guideline Prognostic CBL mutations are associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org). detail...
CBL mutant myelofibrosis not applicable N/A Guideline Prognostic CBL mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). detail...
CBL mutant myelodysplastic/myeloproliferative neoplasm not applicable N/A Clinical Study Prognostic In clinical analyses, mutations in CBL were associated with adverse prognosis in patients with chronic myelomonocytic leukemia (PMID: 26230957, PMID: 23690417, PMID: 19901108). 26230957 19901108 23690417
BRAF G469A CBL C404Y FLT3 exon 14 ins FLT3 D835X acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired CBL C404Y and BRAF G469A (PMID: 31088841). 31088841
CBL dec exp pancreatic ductal carcinoma predicted - sensitive Erlotinib + Gemcitabine Preclinical - Cell line xenograft Emerging In a preclinical study, addition of Tarceva (erlotinib) overcame Gemzar (gemcitabine)-resistance in pancreatic ductal carcinoma cell lines with reduced Cbl expression via shRNA, resulted in decreased viability in cell culture and reduced tumor growth in cell line xenograft models (PMID: 25348515). 25348515
BRAF V600E CBL dec exp high grade glioma predicted - resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, siRNA mediated knockdown of CBL in glioma cell lines harboring BRAF V600E prevented Zelboraf (vemurafenib)-mediated inhibition of cell growth in culture (PMID: 34433654). 34433654
BRAF V600E CBL dec exp high grade glioma predicted - resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, glioma cell lines harboring BRAF V600E and siRNA mediated knockdown of CBL were resistant to treatment with Nerlynx (neratinib) in culture (PMID: 34433654). 34433654
BRAF V600E CBL dec exp high grade glioma predicted - resistant Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, glioma cell lines harboring BRAF V600E and siRNA mediated knockdown of CBL were resistant to treatment with Cotellic (cobimetinib) in culture (PMID: 34433654). 34433654
CBL Y371del FLT3 pos hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Y371del FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Y371del FLT3 pos hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Y371del FLT3 pos hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Y371del FLT3 pos hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Y371del FLT3 pos hematologic cancer sensitive Midostaurin + PRT062607 Preclinical - Cell culture Actionable In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
CBL Q367_E373delinsRLK FLT3 exon 14 ins FLT3 D835X NRAS G12D acute myeloid leukemia predicted - resistant Gilteritinib Case Reports/Case Series Actionable In a clinical study, a patient with acute myeloid leukemia harboring FLT3-ITD and a D835 mutation progressed on Xospata (gilteritinib) treatment and was found to have acquired NRAS G12D and CBL Q367_E373delinsRLK (PMID: 31088841). 31088841