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

Author:

Chisholm Karen M.12ORCID,Smith Jenny3,Heerema‐McKenney Amy E.4,Choi John K.5ORCID,Ries Rhonda E.3,Hirsch Betsy A.6,Raimondi Susana C.7,Wang Yi‐Cheng8,Dang Alice8,Alonzo Todd A.9,Sung Lillian10,Aplenc Richard11,Gamis Alan S.12,Meshinchi Soheil3,Kahwash Samir B.13

Affiliation:

1. Department of Laboratories Seattle Children's Hospital Seattle Washington USA

2. Department of Laboratory Medicine and Pathology University of Washington Medical Center Seattle Washington USA

3. Clinical Research Division Fred Hutchinson Cancer Research Center Seattle Washington USA

4. Pathology and Laboratory Medicine Institute Cleveland Clinic Cleveland Ohio USA

5. Department of Pathology University of Alabama at Birmingham Birmingham Alabama USA

6. Division of Laboratory Medicine University of Minnesota Medical Center, Fairview Minneapolis Minnesota USA

7. Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee USA

8. Children's Oncology Group Monrovia California USA

9. Department of Preventive Medicine, Keck School of Medicine University of Southern California Los Angeles California USA

10. Department of Pediatrics, Division of Hematology/Oncology The Hospital for Sick Children Toronto Ontario Canada

11. Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

12. Children's Mercy Hospitals & Clinics Kansas City Missouri USA

13. Department of Pathology and Laboratory Medicine Nationwide Children's Hospital Columbus Ohio USA

Abstract

AbstractBackgroundAcute 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.MethodsMorphology, 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.ResultsA 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.ConclusionGiven the differences in outcomes, AMkL classification by fusions, cytogenetics, and morphology may be warranted to help in risk stratification and therapeutic options.

Funder

St. Baldrick's Foundation

Publisher

Wiley

Subject

Oncology,Hematology,Pediatrics, Perinatology and Child Health

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