Malignant Progression of an Ancestral Bone Marrow Clone Harboring a CIC-NUTM2A Fusion in Isolated Myeloid Sarcoma

Jennifer L. Kamens, Jinjun Dang, Timothy I. Shaw, Alexander M. Gout, Scott Newman, Kohei Hagiwara, Amelia M.R. Smith, Alyssa N. Obermayer, Sarah Aldridge, Jing Ma, Yang Zhang, Gang Wu, Vasiliki Leventaki, Teresa Santiago, Susana Raimondi, Joy Nakitandwe, Alberto Pappo, Chunliang Li, Jinghui Zhang, Tanja A. Gruber

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow, which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase (RTK) signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.

Original languageEnglish (US)
Pages (from-to)301-306
Number of pages6
JournalMolecular Cancer Research
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2023
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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