Reference Detail

Request Content

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@genomenon.com

Ref Type Journal Article
PMID (39576953)
Authors Smith KER, Acosta-Medina AA, Dasari S, Ranatunga W, Rech KL, Ravindran A, Young JR, McGarrah PW, Ruan GJ, Zanwar SS, Li JJ, Sartori-Valinotti JC, Snider JN, Witzig TE, Goyal G, Go RS, Abeykoon JP
Title Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.
Journal Vol Issue Date Pages Journal Short Title
JCO precision oncology 8 2024 Nov e2400471 JCO Precis Oncol
URL
Abstract Text BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective.We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied through genomic and in silico analyses when applicable, then treated with off-label medications rationally selected on the basis of genomic alterations.Patient 1 had rapidly progressive ECD involving the CNS. A CSF1R in-frame deletion (p.S560_P566del) was identified, and in silico modeling predicted a gain-of-function mutation. This alteration was targeted with pexidartinib, which led to a clinical complete response (CR) within 2 months, and a partial response (PR) on imaging after 3 months. After 15 months, the disease became resistant to pexidartinib and transformed to histiocytic sarcoma. Patient 2 has skin-only involvement of a xanthogranuloma disorder. A KIF5B-FGFR1 fusion was identified on RNA sequencing and targeted with pemigatinib. At 24 months of follow-up, she remains in a clinical PR. Patient 3 has ECD involving the bone marrow, gastrointestinal tract, and subcutaneous tissues. A MEF2C-FLT3 fusion was identified and targeted with sorafenib. He achieved a clinical CR and radiographic PR within 3 months, which has continued for 30 months.We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. 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 on a longer phrase with spaces (i.e. "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
CSF1R F563_P566del deletion unknown CSF1R F563_P566del results in the deletion of four amino acids in the regulatory juxtamembrane domain of the Csf1r protein from amino acids 563 to 566 (UniProt.org). F563_P566del has been identified in the scientific literature (PMID: 39576953), but has not been biochemically characterized and therefore, its effect on Csf1r protein function is unknown (PubMed, Dec 2025).
CSF1R S560_P566del deletion unknown CSF1R S560_P566del results in the deletion of seven amino acids in the regulatory juxtamembrane domain of the Csf1r protein from amino acids 560 to 566 (UniProt.org). S560_P566del has been identified in the scientific literature (PMID: 39576953), but has not been biochemically characterized and therefore, its effect on Csf1r protein function is unknown (PubMed, Dec 2025).
CSF1R S938_Y969del deletion unknown CSF1R S938_Y969del results in the deletion of 32 amino acids in the cytoplasmic domain of the Csf1r protein from amino acids 938 to 969 (UniProt.org). S938_Y969del has been identified in the scientific literature (PMID: 39576953), but has not been biochemically characterized and therefore, its effect on Csf1r protein function is unknown (PubMed, Dec 2025).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CSF1R S560_P566del CSF1R S938_Y969del Erdheim-Chester disease predicted - sensitive Pexidartinib Case Reports/Case Series Actionable In a clinical case study, Turalio (pexidartinib) treatment resulted in a clinical complete response and a partial response on imaging in a patient with Erdheim-Chester disease primarily involving the CNS harboring CSF1R S560_P566del and S938_Y969del (PMID: 39576953). 39576953
CSF1R F563_P566del Erdheim-Chester disease predicted - resistant Pexidartinib Case Reports/Case Series Actionable In a clinical case study, CSF1R F563_P566del was identified at the time of progression, along with loss of the original CSF1R S560_P566del and S938_Y969del mutations, in a patient with Erheim-Chester disease, who originally achieved a partial response with Turalio (pexidartinib) treatment (PMID: 39576953). 39576953