TY - JOUR
T1 - Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation
T2 - A report from the Children's Oncology Group
AU - Chisholm, Karen M.
AU - Smith, Jenny
AU - Heerema-McKenney, Amy E.
AU - Choi, John K.
AU - Ries, Rhonda E.
AU - Hirsch, Betsy A.
AU - Raimondi, Susana C.
AU - Wang, Yi Cheng
AU - Dang, Alice
AU - Alonzo, Todd A.
AU - Sung, Lillian
AU - Aplenc, Richard
AU - Gamis, Alan S.
AU - Meshinchi, Soheil
AU - Kahwash, Samir B.
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/5
Y1 - 2023/5
N2 - Background: Acute myeloid leukemia (AML) with megakaryocytic differentiation (AMkL) is a rare subtype of AML more common in children. Recent literature has identified multiple fusions associated with this type of leukemia. Methods: Morphology, cytogenetics, and genomic sequencing were assessed in patients from Children's Oncology Group trials AAML0531 and AAML1031 with central-pathology review confirmed non-Down syndrome AMkL. The 5-year event-free survival (EFS), overall survival (OS), and RR were evaluated in these AMkL subcategories. Results: A total of 107 cases of AMkL (5.5%) were included. Distinct fusions were identified in the majority: RBM15::MRTFA (20%), CBFA2T3::GLIS2 (16%), NUP98 (10%), KMT2A (7%), TEC::MLLT10 (2%), MECOM (1%), and FUS::ERG (1%); many of the remaining cases were classified as AMkL with (other) myelodysplasia-related changes (MRC). Very few cases had AML-associated somatic mutations. Cases with CBFA2T3::GLIS2 were enriched in trisomy 3 (p =.015) and the RAM phenotype, with associated high CD56 expression (p <.001). Cases with NUP98 fusions were enriched in trisomy 6 (p <.001), monosomy 13/del(13q) (p <.001), trisomy 21 (p =.026), and/or complex karyotypes (p =.026). While different 5-year EFS and OS were observed in AMkL in each trial, in general, those with CBFA2T3::GLIS2 or KMT2A rearrangements had worse outcomes compared to other AMkL, while those with RBM15::MRTFA or classified as AMkl-MRC fared better. AMkL with NUP98 fusions also had poor outcomes in the AAML1031 trial. Conclusion: Given the differences in outcomes, AMkL classification by fusions, cytogenetics, and morphology may be warranted to help in risk stratification and therapeutic options.
AB - Background: Acute myeloid leukemia (AML) with megakaryocytic differentiation (AMkL) is a rare subtype of AML more common in children. Recent literature has identified multiple fusions associated with this type of leukemia. Methods: Morphology, cytogenetics, and genomic sequencing were assessed in patients from Children's Oncology Group trials AAML0531 and AAML1031 with central-pathology review confirmed non-Down syndrome AMkL. The 5-year event-free survival (EFS), overall survival (OS), and RR were evaluated in these AMkL subcategories. Results: A total of 107 cases of AMkL (5.5%) were included. Distinct fusions were identified in the majority: RBM15::MRTFA (20%), CBFA2T3::GLIS2 (16%), NUP98 (10%), KMT2A (7%), TEC::MLLT10 (2%), MECOM (1%), and FUS::ERG (1%); many of the remaining cases were classified as AMkL with (other) myelodysplasia-related changes (MRC). Very few cases had AML-associated somatic mutations. Cases with CBFA2T3::GLIS2 were enriched in trisomy 3 (p =.015) and the RAM phenotype, with associated high CD56 expression (p <.001). Cases with NUP98 fusions were enriched in trisomy 6 (p <.001), monosomy 13/del(13q) (p <.001), trisomy 21 (p =.026), and/or complex karyotypes (p =.026). While different 5-year EFS and OS were observed in AMkL in each trial, in general, those with CBFA2T3::GLIS2 or KMT2A rearrangements had worse outcomes compared to other AMkL, while those with RBM15::MRTFA or classified as AMkl-MRC fared better. AMkL with NUP98 fusions also had poor outcomes in the AAML1031 trial. Conclusion: Given the differences in outcomes, AMkL classification by fusions, cytogenetics, and morphology may be warranted to help in risk stratification and therapeutic options.
KW - CBFA2T3::GLIS2
KW - NUP98 fusions
KW - acute megakaryoblastic leukemia
KW - acute myeloid leukemia
KW - pediatric acute myeloid leukemia
UR - http://www.scopus.com/inward/record.url?scp=85148282020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148282020&partnerID=8YFLogxK
U2 - 10.1002/pbc.30251
DO - 10.1002/pbc.30251
M3 - Article
C2 - 36789545
AN - SCOPUS:85148282020
SN - 1545-5009
VL - 70
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 5
M1 - e30251
ER -