ArticleBlood2016
Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- A Polyproline Type II Peptidomimetic Disrupts a Grb2 SH3C Domain Protein-Protein Interaction Implicated in Breast Cancer.Chembiochem : a European journal of chemical biology · 2025Article
- Article
- Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line.Communications biology · 2021Review
- Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia.Cancers · 2021Review
- Article
- Article
- Synergistic effects of SHP2 and PI3K pathway inhibitors in GAB2-overexpressing ovarian cancer.American journal of cancer research · 2019Article
- Molecular processes involved in B cell acute lymphoblastic leukaemia.Cellular and molecular life sciences : CMLS · 2018Review
- SHP2 is required for BCR-ABL1-induced hematologic neoplasia.Leukemia · 2018Article
- Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Understanding the mechanism of binding between Gab2 and the C terminal SH3 domain from Grb2.Oncotarget · 2017Article
- Targeting BCR-ABL+ stem/progenitor cells and BCR-ABL-T315I mutant cells by effective inhibition of the BCR-ABL-Tyr177-GRB2 complex.Oncotarget · 2017Article
- Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation.Cell reports · 2017Article
- Preclinical approaches in chronic myeloid leukemia: from cells to systems.Experimental hematology · 2017Review
- Gab2 is essential for Bcr-Abl-mediated leukemic transformation and hydronephrosis in a chronic myeloid leukemia mouse model.Leukemia · 2016Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GRB2-associated binding protein 2 (GAB2) as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transducedGab2(-/-)bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors phosphatidylinositol 3-kinase (PI3K) or SRC homology 2-containing phosphotyrosine phosphatase 2 (SHP2). GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph(+)hematologic neoplasms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.