Targeted therapy in juvenile myelomonocytic leukemia: Where are we now?. Issue 11 (12th September 2022)

• Record Type: Journal Article
• Authors: De Vos, Nele; Hofmans, Mattias; Lammens, Tim; De Wilde, Bram; Van Roy, Nadine; De Moerloose, Barbara
• Is Part Of: Pediatric blood & cancer. Volume 69:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-12
• Subjects: JMML -- juvenile myelomonocytic leukemia -- Ras pathway -- targeted therapy; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.29930
• Languages: English
• ISSNs: 1545-5009

Abstract

Abstract: Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive clonal neoplasm of early childhood, classified as an overlap myeloproliferative/myelodysplastic neoplasm by the World Health Organization. In 90% of the patients with JMML, typical initiating mutations in the canonical Ras pathway genes NF1, PTPN11, NRAS, KRAS, and CBL can be identified. Hematopoietic stem cell transplantation (HSCT) currently is the established standard of care in most patients, although long‐term survival is still only 50–60%. Given the limited therapeutic options and the important morbidity and mortality associated with HSCT, new therapeutic approaches are urgently needed. Hyperactivation of the Ras pathway as disease mechanism in JMML lends itself to the use of targeted therapy. Targeted therapy could play an important role in the future treatment of patients with JMML. This review presents a comprehensive overview of targeted therapies already developed and evaluated in vitro and in vivo in patients with JMML.