All Publications

  • Malignant Progression of an Ancestral Bone Marrow Clone Harboring a CIC-NUTM2A Fusion in Isolated Myeloid Sarcoma. Molecular cancer research : MCR Kamens, J. L., Dang, J., Shaw, T. I., Gout, A. M., Newman, S., Hagiwara, K., Smith, A. M., Obermayer, A. N., Aldridge, S., Ma, J., Zhang, Y., Wu, G., Leventaki, V., Santiago, T., Raimondi, S., Nakitandwe, J., Pappo, A., Li, C., Zhang, J., Gruber, T. A. 2023: OF1-OF6


    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.This study illustrates molecular involvement of phenotypically normal bone marrow in myeloid sarcoma, which has significant implications in clinical care. Further, it extends the definition of CIC-rearrangements to include hematologic malignancies and shows evidence of RTK activation that may be exploited therapeutically in cancer(s) driven by these fusions.

    View details for DOI 10.1158/1541-7786.MCR-22-0544

    View details for PubMedID 36637394

  • Therapy-related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature. Pediatric blood & cancer Wintering, A., Smith, S., Fuh, B., Rangaswami, A., Dahl, G., Chien, M., Gruber, T. A., Dang, J., Li, L. S., Lenzen, A., Savelli, S., Dvorak, C. C., Agrawal, A. K., Stieglitz, E. 1800: e29499


    Therapy-related myeloid neoplasms (t-MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy-related myelodysplastic syndrome (t-MDS), therapy-related myeloproliferative neoplasms (t-MPN) and therapy-related acute myeloid leukemia (t-AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy.

    View details for DOI 10.1002/pbc.29499

    View details for PubMedID 34939322

  • Loss of PTEN in Pediatric AML Confers Sensitivity to PARP Inhibition Kamens, J., Cotton, A., Lam, J. W., Dang, J., Seth, A., Hansen, B. S., Pruett-Miller, S. M., Shelat, A., Gruber, T. AMER SOC HEMATOLOGY. 2021