CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy - PubMed (original) (raw)

. 2003 Nov 1;102(9):3093-6.

doi: 10.1182/blood-2003-05-1627. Epub 2003 Jul 3.

Rhett P Ketterling, Stephanie R Brockman, Heather C Flynn, Sarah F Paternoster, Brandon M Shearer, Terra L Reeder, Chin-Yang Li, Nicholas C P Cross, Jan Cools, D Gary Gilliland, Gordon W Dewald, Ayalew Tefferi

Affiliations

• PMID: 12842979
• DOI: 10.1182/blood-2003-05-1627

Free article

CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy

Animesh Pardanani et al. Blood. 2003.

Free article

Abstract

Imatinib mesylate is effective in the treatment of hematologic malignancies that are characterized by either abl- or PDGFR beta- activating mutations. The drug is also active in a subset of patients with eosinophilic disorders and systemic mast cell disease (SMCD). Recently, a novel tyrosine kinase that is generated from fusion of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been identified as a therapeutic target for imatinib mesylate in hypereosinophilic syndrome (HES). We used fluorescence in situ hybridization (FISH) to detect deletion of the CHIC2 locus at 4q12 as a surrogate for the FIP1L1-PDGFRA fusion. CHIC2 deletion was observed in bone marrow cells for 3 of 5 patients with SMCD associated with eosinophilia. Deletion of this locus and expression of the FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) fusion was also documented in enriched eosinophils, neutrophils, or mononuclear cells by both FISH and reverse transcriptase-polymerase chain reaction (RT-PCR) for one patient. While all 3 patients with the FIP1L1-PDGFRA rearrangement achieved a sustained complete response with imatinib mesylate therapy, the other two, both carrying the c-kit Asp816 to Val (Asp816Val) mutation, did not. These observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early hematopoietic progenitor and suggests that the molecular pathogenesis for a subset of SMCD patients is similar to that of HES. Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD.

PubMed Disclaimer

Similar articles

• FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia.
  Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, Ho CL, Li CY, Dewald GW, Tefferi A. Pardanani A, et al. Blood. 2004 Nov 15;104(10):3038-45. doi: 10.1182/blood-2004-03-0787. Epub 2004 Jul 29. Blood. 2004. PMID: 15284118
• The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases.
  La Starza R, Specchia G, Cuneo A, Beacci D, Nozzoli C, Luciano L, Aventin A, Sambani C, Testoni N, Foppoli M, Invernizzi R, Marynen P, Martelli MF, Mecucci C. La Starza R, et al. Haematologica. 2005 May;90(5):596-601. Haematologica. 2005. PMID: 15921374
• Imatinib therapy for hypereosinophilic syndrome and eosinophilia-associated myeloproliferative disorders.
  Pardanani A, Tefferi A. Pardanani A, et al. Leuk Res. 2004 May;28 Suppl 1:S47-52. doi: 10.1016/j.leukres.2003.10.006. Leuk Res. 2004. PMID: 15036941 Review.
• Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib.
  Florian S, Esterbauer H, Binder T, Müllauer L, Haas OA, Sperr WR, Sillaber C, Valent P. Florian S, et al. Leuk Res. 2006 Sep;30(9):1201-5. doi: 10.1016/j.leukres.2005.11.014. Epub 2006 Jan 6. Leuk Res. 2006. PMID: 16406018
• Successful imatinib treatment of cardiac involvement of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia followed by severe hepatotoxicity.
  Arai A, Yan W, Wakabayashi S, Hayashi S, Inazawa J, Miura O. Arai A, et al. Int J Hematol. 2007 Oct;86(3):233-7. doi: 10.1532/IJH97.07032. Int J Hematol. 2007. PMID: 17988989 Review.

Cited by

• Incessant Ventricular Tachycardia: An Atypical Presentation of Chronic Eosinophilic Leukemia.
  Takla A, Shah P, Sbenghe M, Baibhav B, Feitell S. Takla A, et al. JACC Case Rep. 2024 Aug 21;29(16):102461. doi: 10.1016/j.jaccas.2024.102461. eCollection 2024 Aug 21. JACC Case Rep. 2024. PMID: 39295803 Free PMC article.
• Review and Updates on Systemic Mastocytosis and Related Entities.
  Li JY, Ryder CB, Zhang H, Cockey SG, Hyjek E, Moscinski LC, Sagatys E, Song J. Li JY, et al. Cancers (Basel). 2023 Nov 28;15(23):5626. doi: 10.3390/cancers15235626. Cancers (Basel). 2023. PMID: 38067330 Free PMC article. Review.
• French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes.
  Groh M, Rohmer J, Etienne N, Abou Chahla W, Baudet A, Chan Hew Wai A, Chenivesse C, Clisson Rusek I, Cottin V, Decamp M, De Groote P, Delahousse F, Duployez N, Faguer S, Gottrand F, Huang F, Leblanc T, Magnan A, Martin T, Mortuaire G, Néel A, Paris L, Petit A, Rossignol J, Schleinitz N, Soret-Dulphy J, Staumont-Salle D, Terrier B, Terriou L, Viallard JF, Lefèvre G, Kahn JE. Groh M, et al. Orphanet J Rare Dis. 2023 Apr 30;18(1):100. doi: 10.1186/s13023-023-02696-4. Orphanet J Rare Dis. 2023. PMID: 37122022 Free PMC article.
• Novel FIP1L1::KIT fusion in a myeloid neoplasm with eosinophilia, T-lymphoblastic transformation, and dasatinib response.
  Alsouqi A, Kleinberger J, Werner TS, Awan R, Chopra S, Rea B, Aggarwal N, Yatsenko SA, Farah R, Bailey NG. Alsouqi A, et al. Haematologica. 2023 Nov 1;108(11):3181-3185. doi: 10.3324/haematol.2022.282636. Haematologica. 2023. PMID: 37102594 Free PMC article. No abstract available.
• Genomics of PDGFR-rearranged hypereosinophilic syndrome.
  Rheinbay E, Qi M, Bouyssou JM, Oler AJ, Thumm L, Makiya M, Maric I, Klion AD, Lane AA. Rheinbay E, et al. Blood Adv. 2023 Jun 13;7(11):2558-2563. doi: 10.1182/bloodadvances.2022009061. Blood Adv. 2023. PMID: 36652685 Free PMC article. No abstract available.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • GlyGen glycoinformatics resource

• Miscellaneous

  • NCI CPTAC Assay Portal