Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis

Salvatori,Guglielmo; Foligno,Silvia; Sirleto,Pietro; Genovese,Silvia; Russo,Serena; Coletti,Valentina; Dotta,Andrea; Luciani,Matteo

doi:10.3892/ol.2016.5401

Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis

Authors:
- Guglielmo Salvatori
- Silvia Foligno
- Pietro Sirleto
- Silvia Genovese
- Serena Russo
- Valentina Coletti
- Andrea Dotta
- Matteo Luciani
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Affiliations: Department of Neonatology, Bambino Gesù Children's Hospital, I‑00165 Rome, Italy, Department of Genetic Laboratories, Bambino Gesù Children's Hospital, I‑00165 Rome, Italy, Department of Hematology, Bambino Gesù Children's Hospital, I‑00165 Rome, Italy
Published online on: November 21, 2016 https://doi.org/10.3892/ol.2016.5401
Pages: 191-195
Copyright: © Salvatori et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Congenital leukemia is rare disease with an incidence of one to five cases per million births. Transient abnormal myelopoiesis (TAM), also called transient myeloproliferative disorder, is a pre‑leukemia disorder that may occur in Down syndrome (DS) or non‑DS infants. TAM may enter spontaneous remission; however, continual monitoring is required, as this disorder has been observed to develop into acute megakaryoblastic leukemia in 16‑30% of cases. In the literature, 16 cases of TAM in non‑DS infants have been reported. The case presented in the current study is, to the best of our knowledge, the first case of an Italian non‑DS newborn presenting with clinical manifestations of acute leukemia at five days after birth, exhibiting a normal karyotype, trisomy 21 only in blast cells, and spontaneous remission. Chromosomal analyses on peripheral blood cells, bone marrow cells and dermal fibroblasts were conducted using a G‑banding technique, and fluorescence in situ hybridization (FISH) was used to identify the critical regions of DS. Amplification of GATA binding protein 1 (GATA1) exon 2 genomic DNA was performed using polymerase chain reaction. Cytogenetic analysis of 50 peripheral blood cells and dermal fibroblasts from the patient revealed a normal karyotype: 46, XX. Conversely, cytogenetic analysis of the patient's bone marrow revealed an abnormal karyotype 47, XX+21. In order to investigate this result, FISH was performed, which identified the presence of three signals in 70% of the cells and two signals in 30% of bone marrow cells. GATA1 sequencing revealed the substitution of a single base (c.150delG) in exon 2. Seven months after the initial analysis, FISH and cytogenetic analyses of the stimulated/unstimulated peripheral blood cells and bone marrow cells were performed, revealing that each exhibited diploid signals, as observed in a normal karyotype.

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1	Orbach D, Sarnacki S, Brisse HJ, Gauthier-Villars M, Jarreau PH, Tsatsaris V, Baruchel A, Zerah M, Seigneur E, Peuchmaur M and Doz F: Neonatal cancer. Lancet Oncol. 14:e609–e620. 2013. View Article : Google Scholar : PubMed/NCBI
2	Isaacs H Jr: Fetal and neonatal leukemia. J Pediatr Hematol Oncol. 25:348–361. 2003. View Article : Google Scholar : PubMed/NCBI
3	Gamis AS, Alonzo TA, Gerbing RB, Hilden JM, Sorrell AD, Sharma M, Loew TW, Arceci RJ, Barnard D, Doyle J, et al: Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: A report from the children's oncology group study A2971. Blood. 118:6752–6759; quiz 6996. 2011. View Article : Google Scholar : PubMed/NCBI
4	Vyas P and Crispino JD: Molecular insights into Down syndrome-associated leukemia. Curr Opin Pediatr. 19:9–14. 2007. View Article : Google Scholar : PubMed/NCBI
5	Bull MJ: Committee on Genetics: Health supervision for children with Down syndrome. Pediatrics. 128:393–406. 2011. View Article : Google Scholar : PubMed/NCBI
6	Tsai MH, Hou JW, Yang CP, Yang PH, Chu SM, Hsu JF, Chiang MC and Huang HR: Transient myeloproliferative disorder and GATA1 mutation in neonates with and without Down syndrome. Indian J Pediatr. 78:826–832. 2011. View Article : Google Scholar : PubMed/NCBI
7	Schifferli A, Hitzler J, Bartholdi D, Heinimann K, Hoeller S, Diesch T and Kühne T: Transient myeloproliferative disorder in neonates without Down syndrome: Case report and review. Eur J Haematol. 94:456–462. 2015. View Article : Google Scholar : PubMed/NCBI
8	Massey GV, Zipursky A, Chang MN, Doyle JJ, Nasim S, Taub JW, Ravindranath Y, Dahl G and Weinstein HJ: Children's Oncology Group (COG): A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): children's oncology group (COG) study POG-9481. Blood. 107:4606–4613. 2006. View Article : Google Scholar : PubMed/NCBI
9	Klusmann JH, Creutzig U, Zimmermann M, Dworzak M, Jorch N, Langebrake C, Pekrun A, Macakova-Reinhardt K and Reinhardt D: Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood. 111:2991–2998. 2008. View Article : Google Scholar : PubMed/NCBI
10	Apollonsky N, Shende A, Ouansafi I, Brody J, Atlas M and Aygun B: Transient myeloproliferative disorder in neonates with and without Down syndrome: A tale of 2 syndromes. J Pediatr Hematol Oncol. 30:860–864. 2008. View Article : Google Scholar : PubMed/NCBI
11	Sikand GS, Taysi K, Strandjord SE, Griffith R and Vietti TJ: Trisomy 21 in bone marrow cells of a patient with a prolonged preleukemic phase. Med Pediatr Oncol. 8:237–242. 1980. View Article : Google Scholar : PubMed/NCBI
12	Chisté M, Vrotsos E, Zamora C and Martinez A: Chronic lymphocytic leukemia/small lymphocytic lymphoma involving the aortic valve. Ann Diagn Pathol. 17:295–297. 2013. View Article : Google Scholar : PubMed/NCBI
13	Karandikar NJ, Aquino DB, McKenna RW and Kroft SH: Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis. Am J Clin Pathol. 116:204–210. 2001. View Article : Google Scholar : PubMed/NCBI
14	Simons A, Shaffer LG and Hastings RJ: Cytogenetic Nomenclature: Changes in the ISCN 2013 Compared to the 2009 Edition. Cytogenet Genome Res. 141:1–6. 2013. View Article : Google Scholar : PubMed/NCBI
15	Lum SH, Choong SS, Krishnan S, Mohamed Z and Ariffin H: GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder. Singapore Med J. 57:320–324. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wolfe LC, Weinstein HJ and Ferry JA: Case records of the Massachusetts general hospital. Weekly clinicopathological exercises. Case 19–200. A five-day-old girl with leukocytosis and a worsening rash from birth. N Engl J Med. 348:2557–2566. 2003.PubMed/NCBI
17	Ohkawa T, Miyamoto S, Sugie M, Tomizawa D, Imai K, Nagasawa M, Morio T, Mizutani S and Takagi M: Transient abnormal myelopoiesis in non-Down syndrome neonate. Pediatr Int. 57:e14–e17. 2015. View Article : Google Scholar : PubMed/NCBI
18	Mezei G, Sudan M, Izraeli S and Kheifets L: Epidemiology of childhood leukemia in the presence and absence of Down syndrome. Cancer Epidemiol. 38:479–489. 2014. View Article : Google Scholar : PubMed/NCBI
19	Cabelof DC, Patel HV, Chen Q, van Remmen H, Matherly LH, Ge Y and Taub JW: Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome. Blood. 114:2753–2763. 2009. View Article : Google Scholar : PubMed/NCBI
20	Homans AC, Verissimo AM and Vlacha V: Transient abnormal myelopoiesis of infancy associated with trisomy 21. Am J Pediatr Hematol Oncol. 15:392–399. 1993.PubMed/NCBI
21	Ono R, Hasegawa D, Hirabayashi S, Kamiya T, Yoshida K, Yonekawa S, Ogawa C, Hosoya R, Toki T, Terui K, et al: Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children. Eur J Pediatr. 174:525–531. 2015. View Article : Google Scholar : PubMed/NCBI