Mixed Phenotype Acute Leukemia, B/Myeloid (Bilineal and Biphenotypic), With t(2;22)(q35;q12);EWSR1-FEV.
Cell Cycle Proteins
/ genetics
Codon, Nonsense
DNA-Binding Proteins
/ genetics
Female
Humans
Infant
Leukemia, Biphenotypic, Acute
/ genetics
Leukemia, Myeloid, Acute
/ genetics
Oncogene Proteins, Fusion
/ genetics
RNA-Binding Protein EWS
/ genetics
Transcription Factors
/ genetics
Translocation, Genetic
Journal
Journal of pediatric hematology/oncology
ISSN: 1536-3678
Titre abrégé: J Pediatr Hematol Oncol
Pays: United States
ID NLM: 9505928
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
24
11
2019
accepted:
05
08
2020
pubmed:
15
9
2020
medline:
20
5
2021
entrez:
14
9
2020
Statut:
ppublish
Résumé
Ewing sarcoma breakpoint region 1 gene (EWSR1) rearrangements are largely associated with the Ewing sarcoma family of tumors. We report the first case of infantile, mixed phenotype acute leukemia, B/myeloid (bilineal and biphenotypic [B-lymphoid and B-lymphoid/myeloid]), with a t(2;22)(q35;q12). The EWSR1-fifth Ewing variant gene fusion and nonsense mutation in STAG2 were detected by next-generation sequencing and markedly high expression of fifth Ewing sarcoma variant mRNA detected by quantitative reverse transcription polymerase chain reaction. The patient was treated with a combined myeloid/lymphoid leukemia regimen followed by allogeneic stem cell transplant and was in complete remission at 3.8-year follow-up. Our case study underscores the importance of a comprehensive evaluation of acute leukemia and provides insights into the phenotype of EWSR1 rearranged neoplasms in the context of partner genes and cell type.
Sections du résumé
BACKGROUND
Ewing sarcoma breakpoint region 1 gene (EWSR1) rearrangements are largely associated with the Ewing sarcoma family of tumors.
OBSERVATIONS
We report the first case of infantile, mixed phenotype acute leukemia, B/myeloid (bilineal and biphenotypic [B-lymphoid and B-lymphoid/myeloid]), with a t(2;22)(q35;q12). The EWSR1-fifth Ewing variant gene fusion and nonsense mutation in STAG2 were detected by next-generation sequencing and markedly high expression of fifth Ewing sarcoma variant mRNA detected by quantitative reverse transcription polymerase chain reaction. The patient was treated with a combined myeloid/lymphoid leukemia regimen followed by allogeneic stem cell transplant and was in complete remission at 3.8-year follow-up.
CONCLUSIONS
Our case study underscores the importance of a comprehensive evaluation of acute leukemia and provides insights into the phenotype of EWSR1 rearranged neoplasms in the context of partner genes and cell type.
Identifiants
pubmed: 32925408
pii: 00043426-202104000-00026
doi: 10.1097/MPH.0000000000001934
doi:
Substances chimiques
Cell Cycle Proteins
0
Codon, Nonsense
0
DNA-Binding Proteins
0
EWSR1 protein, human
0
FEV protein, human
0
Oncogene Proteins, Fusion
0
RNA-Binding Protein EWS
0
STAG2 protein, human
0
Transcription Factors
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e388-e394Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Fisher C. The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review. Histopathology. 2014;64:134–150.
Janknecht R. EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene. 2005;363:1–14.
Noujaim J, Jones RL, Swansbury J, et al. The spectrum of EWSR1-rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities. Br J Cancer. 2017;116:669–678.
Endo A, Tomizawa D, Aoki Y, et al. EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway. Cancer Sci. 2016;107:1745–1754.
Jakovljevic G, Nakic M, Rogosic S, et al. Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma. Pediatr Blood Cancer. 2010;54:606–609.
Lanocha AA, Zdziarska B. T-cell lymphoblastic leukemia with t(11;22)(q24;q12) and EWSR1 rearrangement. Blood. 2017;129:393.
Hawkins JM, Craig JM, Secker-Walker LM, et al. Ewing’s sarcoma t(11;22) in a case of acute nonlymphocytic leukemia. Cancer Genet Cytogenet. 1991;55:157–162.
Martini A, La Starza R, Janssen H, et al. Recurrent rearrangement of the Ewing’s sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia. Cancer Res. 2002;62:5408–5412.
Borowitz MJ, Bene M-C, Harris NL, et al. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, Siebert R. Acute leukaemias of ambiguous lineage. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised, 4th ed. Lyon, France: IARC Press; 2017:180–187.
Alexander TB, Gu Z, Iacobucci I, et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018;562:373–379.
Liu TH, Tang YJ, Huang Y, et al. Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin. Leukemia. 2017;31:1079–1086.
Ford AM, Ridge SA, Cabrera ME, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature. 1993;363:358–360.
Taub JW, Konrad MA, Ge Y, et al. High frequency of leukemic clones in newborn screening blood samples of children with B-precursor acute lymphoblastic leukemia. Blood. 2002;99:2992–2996.
Hirabayashi S, Ohki K, Nakabayashi K, et al. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica. 2017;102:118–129.
Crompton BD, Stewart C, Taylor-Weiner A, et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 2014;4:1326–1341.
Milione M, Gasparini P, Sozzi G, et al. Ewing sarcoma of the small bowel: a study of seven cases, including one with the uncommonly reported EWSR1-FEV translocation. Histopathology. 2014;64:1014–1026.
Codrington R, Pannell R, Forster A, et al. The Ews-ERG fusion protein can initiate neoplasia from lineage-committed haematopoietic cells. PLoS Biol. 2005;3:e242.
Cho J, Shen H, Yu H, et al. Ewing sarcoma gene Ews regulates hematopoietic stem cell senescence. Blood. 2011;117:1156–1166.
Torchia EC, Boyd K, Rehg JE, et al. EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice. Mol Cell Biol. 2007;27:7918–7934.
Takahashi K, Wang F, Morita K, et al. Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nat Commun. 2018;9:2670.
Greaves MF, Chan LC, Furley AJ, et al. Lineage promiscuity in hemopoietic differentiation and leukemia. Blood. 1986;67:1–11.
Smith LJ, Curtis JE, Messner HA, et al. Lineage infidelity in acute leukemia. Blood. 1983;61:1138–1145.
Orgel E, Alexander TB, Wood BL, et al. Mixed-phenotype acute leukemia: a cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force. Cancer. 2020;126:593–601.
Yan L, Ping N, Zhu M, et al. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica. 2012;97:1708–1712.
Matutes E, Pickl WF, Van’t Veer M, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011;117:3163–3171.
Deffis-Court M, Alvarado-Ibarra M, Ruiz-Arguelles GJ, et al. Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in Mexico. Ann Hematol. 2014;93:595–601.
Liu QF, Fan ZP, Wu MQ, et al. Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens. Ann Hematol. 2013;92:679–687.
Hrusak O, de Haas V, Stancikova J, et al. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood. 2018;132:264–276.
Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481:157–163.