DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20173806

Pediatric acute myeloid leukemia with t(8;21) variant: what is the value on clinical outcome?

Juliana C. Abreu, Raissa M. Fontes, Jesamar C. Matos, Fátima G. Jorge, Diego S. Lima

Abstract


Acute myeloid leukemia (AML) is characterized by clonal expansion of undifferentiated myeloid precursors that results in the bone marrow (BM) failure. Some cytogenetic alterations can be used to predict the prognosis of the disease. AML with t(8;21), presenting RUNX1/RUNX1T1 gene fusion, is associated to favorable prognosis and it is one of most prevalent structural abnormalities in pediatric AML. Variants of t(8;21) has been described, though the prognostic value of these changes remains controversial, especially in pediatric patients. Thereby, we report a pediatric patient with AML with RUNX1/RUNX1T1 fusion presenting the variant t(1;21;8). The diagnosis was confirmed by myelogram, immunophenotyping, cytogenetics and molecular biology. After the diagnosis, the patient was subjected to chemotherapy and submitted to related allogeneic BM transplant. Until this date, the patient has no clinical complaints, predicting a favorable outcome. The register of variants and its proper follow up contributes to a better understanding of the mechanisms involved in these rearrangements and provides information that may be relevant for an appropriate classification and risk stratification of these patients.


Keywords


Acute myeloid leukemia, RUNX1/RUNX1T1, t(8;21) variant

Full Text:

PDF

References


Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. World Healthy Organization (WHO): classification of tumours of haematopoietic and lymphoid tissues; 2008.

Longo DL, Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373:1136-52.

Saultz JN, Garzon R. Acute myeloid leukemia: a concise review. J Clin Med. 2016;5:33-51.

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, et al. Proposed revised criteria for the classification of acute myeloid leukemia: A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103:620-5.

Manola KN. Cytogenetics of pediatric acute myeloid leukemia. Eur J Haematol 2009;83:391-405.

Müller AMS, Duque J, Shizuru JA, Lübbert M. Complementing mutations in core binding factor leukemias: from mouse models to clinical applications. Oncogene. 2008;27:5759-73.

Hatlen MA, Wang L, Nimer SD. ML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches. Front Med. 2012;6:248-62.

Mosna F, Gottardi M. Stem cell modeling of core binding factor acute myeloid leukemia. Stem Cells International; 2016.

Huang L, Abruzzo LV, Valbuena JR, Medeiros LJ, Lin P. Acute myeloid leukemia associated with variant t(8;21) detected by conventional cytogenetic and molecular studies. Am J Clin Pathol. 2006;125:267-72.

Ahmad F, Kokate P, Chheda P, Dalvi R, Das BR, Mandava S, Molecular cytogenetic findings in a three-way novel variant of t(1;8 21)(p35;q22;q22): a unique relocation of the AML1/ETO fusion gene 1p35 in AML-M2. Cancer Genet Cytogenet. 2008;180:153-7.

Bae SY, Kim JS, Ryeu BJ, Lee KN, Lee CK, Kim YK, et al. Acute myeloid leukemia (AML-M2) associated with variant t(8;21): report of three cases. Cancer Genet Cytogenet. 2010;199:31-7.

Yamamoto K, Yakushijin K, Funakoshi Y, Sanada Y, Kawamoto S, Matsuoka H, et al. A new complex translocation t(8;11;21)(q22;q24;q22) in acute myeloid leukemia with RUNX1/RUNX1T1. J Clin Exp Hematop. 2014;167-70.

Matos RRC, De Figueiredo AF, Liehr T, Alhourani E, De Souza MT, Binato R, et al. A novel three-way variant t(8;13;21)(q22;q33;q22) in a child with acute myeloid leukemia with RUNX1/RUNX1T1: the contribution of molecular approaches for revealing t(8;21) variants. Acta Haematol 2015;134:243-5.

Van Dongen JJM, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, et al. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Leukemia 1999;13:1901-28.

Shaffer LG, McGowan-Jordan J, Schmid M. ISCN 2013: an international system for human cytogenetic nomenclature. Karger Medical and Scientific Publishers; 2013.

Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Fleischhack G, Graf N, et al. Randomized trial comparing liposomal daunoru-bicin with idarubicin as induction for pediat-ric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122:37-43.

Rubnitz JE, Raimondi SC, Halbert AR, Tong X, Srivastava DK, Razzouk BI, et al. Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution’s experience. Leukemia 2002;16:2072-7.

Kakosaiou K, Daraki A, Zomas A, Manola KN. A novel variant translocation t(8;16;21) (q22;q24;q22) in acute myeloid leukemia expressing both myeloid and lymphoid markers. Hospital Chronicles. 2015;10:174-6.

Kelly MJ, Meloni-Ehrig AM, Manley PE, Altura RA: Poor outcome in a pediatric patient with acute myeloid leukemia associated with a variant t(8;21) and trisomy 6. Cancer Genet Cytogenet 2009;189:48-52.

Vunditi BR, Kerketta L, Madkaikar M, Jijina F, Ghosh K. Three way translocation in a new variant of t(8;21) acute myeloid leukemia involving Xp22. Indian J Cancer 2008;45:30-32.

Kim H, Moon HW, Hur M, Yun YM, Lee MH. Acute myeloid leukemia with a RUNX1-RUNX1T1 t(1;21;8)(q21;q22;q22) novel variant: a case report and review of the literature. Acta Haematol. 2011;125:237-41.

Gmidène A, Frikha R, Sennana H, Elghezal H, Elloumi M, Saad A. T (1; 21; 8)(p34; q22; q22): a novel variant of t (8; 21) in acute myeloblastic leukemia with maturation. Medic Oncol. 2011;28:509-12.

Tirado CA, Chen W, Valdez FJ, Henderson S, Doolittle J, Garcia R, et al. Acute myeloid leukemia (M2) with a cryptic RUNX1/RUNX1T1 t (1; 21; 8)(p36; q22; q22) variant. Cancer Genet Cytogenet. 2009;193:67-9.

Rubnitz JE, Lensing S, Zhou Y, Sandlund JT, Razzouk BI, Ribeiro RC, et al. Death during induction therapy and first remission of acute leukemia in childhood. Cancer 2004;101:1677-84.

Odero MD, Vizmanos JL, Rom´n JP, Lahortiga I, Panizo C, Calasanz MJ, et al. A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome. Genes, chromosomes and cancer. 2002;35:11-9.

Nishikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, et al. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood. 2003;102:3323-32.

Min YH, Eom JI, Cheong JW, Maeng HO, Kim JY, Jeung HK, et al. Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable. Leukemia 2003;17:995-7.

Sasaki O, Meguro K, Tohmiya Y, Funato T, Shibahara S. Sasaki T. Altered expression of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukaemia. Br J Haematol. 2002;119:940-8.