Functional consequence and therapeutic targeting of cryptic ALK fusions in monosomy 7 acute myeloid leukemia

Makia K Manselle; Rhonda E Ries; Tiffany Hylkema; Amanda Leonti; Danielle C Kirkey; Scott N Furlan; Soheil Meshinchi

doi:10.1002/pbc.30180

Functional consequence and therapeutic targeting of cryptic ALK fusions in monosomy 7 acute myeloid leukemia

Pediatr Blood Cancer. 2023 Apr;70(4):e30180. doi: 10.1002/pbc.30180. Epub 2023 Jan 31.

Authors

Makia K Manselle^{1

2}, Rhonda E Ries¹, Tiffany Hylkema¹, Amanda Leonti¹, Danielle C Kirkey^{1

2}, Scott N Furlan¹, Soheil Meshinchi^{1

2}

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
² Clinical Research Division, University of Washington, Seattle, Washington, USA.

PMID: 36720638
DOI: 10.1002/pbc.30180

Abstract

Acute myeloid leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations, which can influence response to therapy. Monosomy 7 is a rare subset within pediatric AML (prevalence of <2%) that is highly associated with poor outcomes. Fusions involving the anaplastic tyrosine kinase (ALK) gene were exclusively identified in 14.3% of this high-risk cohort, while absent across all other AML. Given the dismal outcomes of monosomy 7, we evaluated the use of crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients with ALK fusions. Our findings suggest that crizotinib may serve as a novel therapy for these patients.

Keywords: AML; cancer genetics; chemotherapy; cytogenetics; hematology/oncology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Chromosome Deletion
Crizotinib / therapeutic use
Humans
Leukemia, Myeloid, Acute* / drug therapy
Protein Kinase Inhibitors / therapeutic use
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / therapeutic use

Substances

Crizotinib
Protein Kinase Inhibitors
Receptor Protein-Tyrosine Kinases
ALK protein, human

Supplementary concepts

Chromosome 7, monosomy