Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (28031554)
Authors Rohrabaugh S, Kesarwani M, Kincaid Z, Huber E, Leddonne J, Siddiqui Z, Khalifa Y, Komurov K, Grimes HL, Azam M
Title Enhanced MAPK signaling is essential for CSF3R-induced leukemia.
Journal Leukemia
Vol 31
Issue 8
Date 2017 08
URL
Abstract Text Both membrane-proximal and truncation mutations in CSF3R have recently been reported to drive the onset of chronic neutrophilic leukemia (CNL). Here we show that although truncation mutation alone cannot induce leukemia, both proximal and compound mutations (proximal and truncation mutations on same allele) are leukemogenic with a disease latency of 90 and 23 days, respectively. Comparative whole-genome expression profiling and biochemical experiments revealed that induced expression of Mapk adaptor protein Ksr1 and enhanced Mapk signaling are crucial to leukemogenesis by CSF3R proximal and compound mutants. Moreover, inhibition of Mek1/2 by trametinib alone is sufficient to suppress leukemia induced by both CSF3R proximal and ruxolitinib-resistant compound mutations. Together, these findings elucidate a Mapk-dependent mechanism of CSF3R-induced pathogenesis, and they establish the rationale for clinical evaluation of MEK1/2 inhibition in CNL.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CSF3R T618I CSF3R W791* hematologic cancer predicted - resistant AZD1480 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R W791* were resistant to treatment with AZD1480 in culture (PMID: 28031554). 28031554
CSF3R T618I hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R T618I demonstrated resistance to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554
CSF3R W791* hematologic cancer predicted - sensitive AZD1480 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R W791** were sensitive to treatment with AZD1480 in culture, demonstrating decreased cell survival (PMID: 28031554). 28031554
CSF3R T618I CSF3R W791* hematologic cancer predicted - resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R W791* were resistant to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell survival (PMID: 28031554). 28031554
CSF3R W791* hematologic cancer predicted - sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R W791* were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell survival (PMID: 28031554). 28031554
CSF3R T618I CSF3R Q741* hematologic cancer predicted - resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R Q741* were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 28031554). 28031554
CSF3R T618I CSF3R Q741* hematologic cancer predicted - resistant AZD1480 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R Q741* were resistant to treatment with AZD1480 in culture (PMID: 28031554). 28031554
CSF3R Q741* hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R Q741* demonstrated resistance to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554
CSF3R Q741* hematologic cancer predicted - sensitive AZD1480 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R Q741* were sensitive to treatment with AZD1480 in culture, demonstrating decreased cell survival (PMID: 28031554). 28031554
CSF3R T618I CSF3R Q741* hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R Q741* were resistant to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554
CSF3R Q741* hematologic cancer predicted - sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R Q741* were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell survival (PMID: 28031554). 28031554
CSF3R T618I CSF3R W791* hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing CSF3R T618I and CSF3R W791* were resistant to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554
CSF3R W791* hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R W791* demonstrated resistance to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554