TY - JOUR
T1 - Myeloid/lymphoid neoplasms with FLT3 rearrangement
AU - Tang, Guilin
AU - Tam, Wayne
AU - Short, Nicholas J.
AU - Bose, Prithviraj
AU - Wu, David
AU - Hurwitz, Stephanie N.
AU - Bagg, Adam
AU - Rogers, Heesun J.
AU - Hsi, Eric D.
AU - Quesada, Andres E.
AU - Wang, Wei
AU - Miranda, Roberto N.
AU - Bueso-Ramos, Carlos E.
AU - Medeiros, L. Jeffrey
AU - Nardi, Valentina
AU - Hasserjian, Robert P.
AU - Arber, Daniel A.
AU - Orazi, Attilio
AU - Foucar, Kathryn
AU - Wang, Sa A.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85105826332&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105826332&partnerID=8YFLogxK
U2 - 10.1038/s41379-021-00817-7
DO - 10.1038/s41379-021-00817-7
M3 - Article
C2 - 33990705
AN - SCOPUS:85105826332
SN - 0893-3952
VL - 34
SP - 1673
EP - 1685
JO - Modern Pathology
JF - Modern Pathology
IS - 9
ER -