Acute erythroid leukemia is enriched in NUP98 fusions: a report from the Children's Oncology Group.

TitleAcute erythroid leukemia is enriched in NUP98 fusions: a report from the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2020
AuthorsChisholm KM, Heerema-McKenney AE, Choi JK, Smith J, Ries RE, Hirsch BA, Raimondi SC, Alonzo TA, Wang Y-C, Aplenc R, Sung L, Gamis AS, Meshinchi S, Kahwash SB
JournalBlood Adv
Volume4
Issue23
Pagination6000-6008
Date Published2020 Dec 08
ISSN2473-9537
Abstract

Acute erythroid leukemia (AEL) is a rare subtype of acute myeloid leukemia (AML) primarily affecting older adults and was previously classified into erythroid/myeloid and pure erythroid subtypes. In this pediatric AEL study, we evaluated morphologic, immunophenotypic, cytogenetic, molecular, and clinical data of 24 (1.2%) cases from all cases undergoing central pathology review in Children's Oncology Group trials AAML0531 and AAML1031. Of 24 cases, 5 had a pure erythroid phenotype, and 19 had an erythroid/myeloid phenotype. NUP98 fusions were highly enriched in patients with AEL, occurring in 7 of 22 cases for which molecular data were available (31.8% vs 6.7% in other AML subtypes). Of 5 cases of pure erythroid leukemias (PELs), 3 had NUP98 fusions, and 4 had complex karyotypes. Erythroid/myeloid leukemias were reclassified by using the 2017 World Health Organization hematopathology classification as: myelodysplastic syndrome (MDS) with excess blasts-1 (n = 3), MDS with excess blasts-2 (n = 7), AML (nonerythroid, n = 5), and unknown MDS/AML (n = 4); the 5 cases of nonerythroid AML included 1 with an NUP98-NSD1 fusion, 2 with myelodysplasia-related changes, and 1 with a complex karyotype. Three cases of MDS with excess blasts-2 also had NUP98 rearrangements. WT1 mutations were present in 5 of 14 cases, all erythroid/myeloid leukemia. Outcomes assessment revealed statistically poorer overall survival (5-year, 20% ± 36% vs 66% ± 23%; P = .004) and event-free survival (5-year, 20% ± 36% vs 46% ± 23%; P = .019) for those with PEL than those with erythroid/myeloid leukemia. Our study supports that AEL is a morphologically and genetically heterogeneous entity that is enriched in NUP98 fusions, with the pure erythroid subtype associated with particularly adverse outcomes.

DOI10.1182/bloodadvances.2020002712
Alternate JournalBlood Adv
PubMed ID33284945
PubMed Central IDPMC7724911
Grant ListU10 CA098413 / CA / NCI NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States
U10 CA180899 / CA / NCI NIH HHS / United States