Myeloid/Lymphoid Neoplasms with FLT3 Rearrangement

Authors

• Guilin Tang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAFollow
• Wayne Tam, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA
• Nicholas J. Short, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Prithviraj Bose, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• David Wu, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
• Stephanie N. Hurwitz, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
• Adam Bagg, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
• Heesun J. Rogers, Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA
• Eric D. Hsi, Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA
• Andres E. Quesada, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Wei Wang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Roberto N. Miranda, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Carlos E. Bueso-Ramos, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• L Jeffrey Medeiros, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
• Valentina Nardi, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
• Robert P. Hasserjian, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
• Daniel A. Arber, Department of Pathology, University of Chicago, Chicago, IL, USA
• Attilio Orazi, Department of Pathology, Texas Tech University Health Sciences Center, El Paso, TX, USA
• Kathryn Foucar, Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, USA
• Sa A. Wang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAFollow

Document Type

Article

Publication Date

9-1-2021

Abstract

Myeloid/lymphoid neoplasms (M/LN) with 13q12/FLT3 rearrangement have been suggested as candidates for possible inclusion in the World Health Organization classification group of M/LN with eosinophilia (M/LN-eo). We report 12 patients with confirmed FLT3 rearrangement, six with t(12;13)/ETV6-FLT3; one with ins(13;22)/BCR-FLT3; and five with an unconfirmed partner gene located on chromosome bands 2p16, 3q27, 5q15, 5q35, and 7q36. Disease presentations were heterogeneous, including lymphoblastic leukemia/lymphoma, myeloid sarcoma, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, and myelodysplastic syndrome. However, some common features were observed, such as extramedullary involvement (n = 7, 58%), associated eosinophilia in blood, bone marrow, or tissue (n = 8, 67%), multilineage involvement, either as biphasic myeloid/lymphoid neoplasms (n = 2) or mixed phenotype acute leukemia (n = 2). Mutations were detected in 4/8 (50%) patients by next-generation sequencing. None (0/10) had FLT3 or KIT mutations. Eleven patients received disease-based chemotherapy or hypomethylating agents, three received FLT3 inhibitors, and five patients proceeded to hematopoietic stem cell transplant. Together with a review of 16 cases published in the literature, it is apparent that M/LNs with FLT3 rearrangement show disease features reminiscent of members in the category of M/LN-eo with PDGFRA, PDGFRB, FGFR1, and PCM1/JAK2 rearrangement, characterized by a specific gene rearrangement, frequent eosinophilia, multi-lineage involvement and therapeutic benefit from kinase inhibitors.

Recommended Citation

Tang G, Tam W, Short NJ, Bose P, Wu D, Hurwitz SN, Bagg A, Rogers HJ, Hsi ED, Quesada AE, Wang W, Miranda RN, Bueso-Ramos CE, Medeiros LJ, Nardi V, Hasserjian RP, Arber DA, Orazi A, Foucar K, Wang SA. Myeloid/lymphoid neoplasms with FLT3 rearrangement. Mod Pathol. 2021 Sep;34(9):1673-1685. doi: 10.1038/s41379-021-00817-7. Epub 2021 May 14. PMID: 33990705.