Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group.

Autor: Chisholm KM; Department of Laboratories, Seattle Children's Hospital, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, Washington, USA., Smith J; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Heerema-McKenney AE; Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA., Choi JK; Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Ries RE; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Hirsch BA; Division of Laboratory Medicine, University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota, USA., Raimondi SC; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Wang YC; Children's Oncology Group, Monrovia, California, USA., Dang A; Children's Oncology Group, Monrovia, California, USA., Alonzo TA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Sung L; Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada., Aplenc R; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Gamis AS; Children's Mercy Hospitals & Clinics, Kansas City, Missouri, USA., Meshinchi S; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Kahwash SB; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2023 May; Vol. 70 (5), pp. e30251. Date of Electronic Publication: 2023 Feb 15.
DOI: 10.1002/pbc.30251
Abstrakt: 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.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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