Abstract
Chromosome translocation t(16;21)(q24;q22)/RUNX1-RUNX1T3 is an infrequent but recurrent chromosomal abnormality identified in myeloid neoplasms, with only 25 cases have been reported to date. Here, we report eight cases (six women and two men) of myeloid neoplasms associated with t(16;21)(q24;q22): five with therapy-related myeloid neoplasms, two with relapsed acute myeloid leukemia (AML), and one with blast phase of chronic myeloid leukemia. Morphologic and immunophenotypic features include granulocytic dysplasia, blasts with prominent perinuclear hof, large orange-pink granules, long and slim Auer rods, and aberrant expression of CD19. Six patients received AML-based regimens, and five achieved complete remission after initial induction therapy. Our study suggests that myeloid neoplasm with t(16;21)/RUNX1-RUNX1T1 resembles AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1, in regard to morphology, immunophenotype, and response to therapy. Therefore, the clinical management of AML with t(8;21) may provide the best model for patients with myeloid neoplasms with t(16;21).
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De Braekeleer E, Douet-Guilbert N, Morel F et al (2011) RUNX1 translocations and fusion genes in malignant hemopathies. Future Oncol 7:77–91
Ito Y, Bae SC, Chuang LS (2015) The RUNX family: developmental regulators in cancer. Nat Rev Cancer 15:81–95
Yamagata T, Maki K, Mitani K (2005) Runx1/UAML1 in normal and abnormal hematopoiesis. Int J Hematol 82:1–8
Gamou T, Kitamura E, Hosoda F, Shimizu K, Shinohara K, Hayashi Y, Nagase T, Yokoyama Y, Ohki M (1998) The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Blood 91:4028–4037
Athanasiadou A, Stalika E, Sidi V, Papaioannou M, Gaitatzi M, Anagnostopoulos A (2011) RUNX1-MTG16 fusion gene in de novo acute myeloblastic leukemia with t(16;21)(q24;q22). Leuk Lymphoma 52:145–147
De Braekeleer E, Douet-Guilbert N, Le Bris MJ et al (2008) RUNX1-MTG16 fusion gene in acute myeloblastic leukemia with t(16;21)(q24;q22): case report and review of the literature. Cancer Genet Cytogenet 185:47–50
Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL (1989) Cytogenetics of childhood acute nonlymphocytic leukemia. Cancer Genet Cytogenet 40:13–27
Jeandidier E, Dastugue N, Mugneret F, Lafage-Pochitaloff M, Mozziconacci MJ, Herens C, Michaux L, Verellen-Dumoulin C, Talmant P, Cornillet-Lefebvre P, Luquet I, Charrin C, Barin C, Collonge-Rame MA, Pérot C, van den Akker J, Grégoire MJ, Jonveaux P, Baranger L, Eclache-Saudreau V, Pagès MP, Cabrol C, Terré C, Berger R, Groupe Français de Cytogénétique Hématologique (GFCH) (2006) Abnormalities of the long arm of chromosome 21 in 107 patients with hematopoietic disorders: a collaborative retrospective study of the Groupe Francais de Cytogenetique Hematologique. Cancer Genet Cytogenet 166:1–11
Shimada M, Ohtsuka E, Shimizu T, Matsumoto T, Matsushita K, Tanimoto F, Kajii T (1997) A recurrent translocation, t(16;21)(q24;q22), associated with acute myelogenous leukemia: identification by fluorescence in situ hybridization. Cancer Genet Cytogenet 96:102–105
Zatkova A, Fonatsch C, Sperr WR, Valent P (2007) A patient with de novo AML M1 and t(16;21) with karyotype evolution. Leuk Res 31:1319–1321
Park IJ, Park JE, Kim HJ, Jung HJ, Lee WG, Cho SR (2010) Acute myeloid leukemia with t(16;21)(q24;q22) and eosinophilia: case report and review of the literature. Cancer Genet Cytogenet 196:105–108
Kawashima N, Shimada A, Taketani T, Hayashi Y, Yoshida N, Matsumoto K, Takahashi Y, Kojima S, Kato K (2012) Childhood acute myeloid leukemia with bone marrow eosinophilia caused by t(16;21)(q24;q22). Int J Hematol 95:577–580
Traweek ST, Slovak ML, Nademanee AP, Brynes RK, Niland JC, Forman SJ (1994) Clonal karyotypic hematopoietic-cell abnormalities occurring after autologous bone-marrow transplantation for Hodgkin’s-disease and non-Hodgkin’s-lymphoma. Blood 84:957–963
Berger R, Le Coniat M, Romana SP, Jonveaux P (1996) Secondary acute myeloblastic leukemia with t(16;21)(q24;q22) involving the AML1 gene. Hematol Cell Ther 38:183–186
Kondoh K, Nakata Y, Furuta T, Hosoda F, Gamou T, Kurosawa Y, Kinoshita A, Ohki M, Tomita Y, Mori T (2002) A pediatric case of secondary leukemia associated with t(16;21)(q24;q22) exhibiting the chimeric AML1-MTG16 gene. Leuk Lymphoma 43:415–420
Salomon-Nguyen F, Busson-Le Coniat M, Lafage Pochitaloff M et al (2000) AML1-MTG16 fusion gene in therapy-related acute leukemia with t(16;21)(q24;q22): two new cases. Leukemia 14:1704–1705
Ottone T, Hasan SK, Montefusco E, Curzi P, Mays AN, Chessa L, Ferrari A, Conte E, Noguera NI, Lavorgna S, Ammatuna E, Divona M, Bovetti K, Amadori S, Grimwade D, Lo-Coco F (2009) Identification of a potential “hotspot” DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation. Genes Chromosom Cancer 48:213–221
Nylund SJ, Ruutu T, Saarinen U, Knuutila S (1994) Metaphase fluorescence in-situ hybridization (FISH) in the follow-up of 60 patients with hematopoietic malignancies. Br J Haematol 88:778–783
Takeda K, Shinohara K, Kameda N, Ariyoshi K (1998) A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide. Int J Hematol 67:179–186
La Starza R, Sambani C, Crescenzi B et al (2001) AML1/MTG16 fusion gene from a t(16;21)(q24;q22) translocation in treatment-induced leukemia after breast cancer. Haematologica 86:212–213
Boils CL, Mohamed AN (2008) t(16;21)(q24;q22) in acute myeloid leukemia: case report and review of the literature. Acta Haematol 119:65–68
Woodham P (2017) Mixed phenotype treatment-related acute myeloid leukemia. In: Wolff DJ (ed). SH/EAHP 2017 workshop, p case #83
McGowan-Jordan J SA, Schmid M (eds) (2016) An international system for human cytogenetic normenclature (ISCN 2016), recommendations of the international standing committee on human cytogenetic normenclature. Karger
Kanagal-Shamanna R, Luthra R, Yin CC, Patel KP, Takahashi K, Lu X, Lee J, Zhao C, Stingo F, Zuo Z, Routbort MJ, Singh RR, Fox P, Ravandi F, Garcia-Manero G, Medeiros LJ, Bueso-Ramos CE (2016) Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2. ASXL1 NRAS Oncotarget 7:14251–14258
Lavallee VP, Lemieux S, Boucher G, Gendron P, Boivin I, Armstrong RN, Sauvageau G, Hebert J (2016) RNA-sequencing analysis of core binding factor AML identifies recurrent ZBTB7A mutations and defines RUNX1-CBFA2T3 fusion signature. Blood 127:2498–2501
Slovak ML, Bedell V, Popplewell L, Arber DA, Schoch C, Slater R (2002) 21q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: report from an international workshop. Genes Chromosomes Cancer 33:379–394
Schnittger S, Bacher U, Haferlach C, Kern W, Haferlach T (2007) Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients. Leukemia 21:725–731
Arber DA, Brunning RD, Le Beau MM et al (2017) Acute myeloid leukemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoeitic and lymphoid tissue (revised 4th edition). IARC, Lyon
Valbuena JR, Medeiros LJ, Rassidakis GZ, Hao S, Wu CD, Chen L, Lin P (2006) Expression of B cell-specific activator protein/PAX5 in acute myeloid leukemia with t(8;21)(q22;q22). Am J Clin Pathol 126:235–240
Borowitz MJBM, Harris NL et al (2017) Acute leukemias of ambiguous lineage. In: CE SSH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (eds) WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition). IARC, Lyon
Tiacci E, Pileri S, Orleth A, Pacini R, Tabarrini A, Frenguelli F, Liso A, Diverio D, Lo-Coco F, Falini B (2004) PAX5 expression in acute leukemias: higher B-lineage specificity than CD79a and selective association with t(8;21)-acute myelogenous leukemia. Cancer Res 64:7399–7404
Gustafson SA, Lin P, Chen SS, Chen L, Abruzzo LV, Luthra R, Medeiros LJ, Wang SA (2009) Therapy-related acute myeloid leukemia with t(8;21) (q22;q22) shares many features with de novo acute myeloid leukemia with t(8;21)(q22;q22) but does not have a favorable outcome. Am J Clin Pathol 131:647–655
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Liu, H., Wang, S.A., Schlette, E.J. et al. Myeloid neoplasms with t(16;21)(q24;q22)/RUNX1-RUNX1T3 mimics acute myeloid leukemia with RUNX1-RUNX1T1. Ann Hematol 97, 1775–1783 (2018). https://doi.org/10.1007/s00277-018-3389-3
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DOI: https://doi.org/10.1007/s00277-018-3389-3