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.

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