{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:04:56Z","timestamp":1753869896242,"version":"3.41.2"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with Down syndrome (DS) are commonly affected by a pre\u2010leukemic disorder known as transient abnormal myelopoiesis (TAM). This condition usually undergoes spontaneous remission within the first 2\u00a0months after birth; however, in children under 5, 20%\u201330% of cases evolve to myeloid leukemia of Down syndrome (ML\u2010DS). TAM and ML\u2010DS are caused by co\u2010operation between trisomy 21 and acquired mutations in the <jats:italic>GATA1<\/jats:italic> gene. Currently, only next\u2010generation sequencing (NGS)\u2010based methodologies are sufficiently sensitive for diagnosis in samples with small <jats:italic>GATA1<\/jats:italic> mutant clones (\u226410% blasts). Alternatively, this study presents research on a new, fast, sensitive, and inexpensive high\u2010resolution melting (HRM)\u2010based diagnostic approach that allows the detection of most cases of <jats:italic>GATA1<\/jats:italic> mutations, including silent TAM. The algorithm first uses flow cytometry for blast count, followed by HRM and Sanger sequencing to search for mutations on exons 2 and 3 of <jats:italic>GATA1<\/jats:italic>. We analyzed 138 samples of DS patients: 110 of asymptomatic neonates, 10 suspected of having TAM, and 18 suspected of having ML\u2010DS. Our algorithm enabled the identification of 33 mutant samples, among them five cases of silent TAM (5\/110) and seven cases of ML\u2010DS (7\/18) with blast count \u226410%, in which <jats:italic>GATA1<\/jats:italic> alterations were easily detected by HRM. Depending on the type of genetic variation and its location, our methodology reached sensitivity similar to that obtained by NGS (0.3%) at a considerably reduced time and cost, thus making it accessible worldwide.<\/jats:p>","DOI":"10.1002\/pbc.29866","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T15:45:25Z","timestamp":1655912725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A sensitive and inexpensive high\u2010resolution melting\u2010based testing algorithm for diagnosis of transient abnormal myelopoiesis and myeloid leukemia of Down syndrome"],"prefix":"10.1002","volume":"69","author":[{"given":"Ricardo","family":"Camargo","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Agenor","family":"de Castro Moreira dos Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"},{"name":"Laborat\u00f3rio Central de Sa\u00fade P\u00fablica do Distrito Federal  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6397-1259","authenticated-orcid":false,"given":"Bruna","family":"C\u00e2ndido Guido","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Lemos Mendanha Cavalcante","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Carolina","family":"Silva Dias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob\u00e9ria","family":"Mendon\u00e7a de Pontes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Magalh\u00e3es Furtado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0221-6011","authenticated-orcid":false,"given":"Cristiane","family":"Feitosa Salviano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valdenize","family":"Tiziani","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Carlos","family":"Martins C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isis Maria","family":"Quezado Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional Hospital da Crian\u00e7a de Bras\u00edlia Jos\u00e9 Alencar  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-163501"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0854-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05264-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200006000-00002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-515148"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2013.07.008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-016-0338-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3679"},{"issue":"2","key":"e_1_2_10_10_1","first-page":"76","article-title":"Down syndrome and leukemia: insights into leukemogenesis and translational targets","volume":"4","author":"Mateos MK","year":"2015","journal-title":"Transl Pediatr"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-687889"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205326"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.19-5-397"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-342774"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902829433"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12308-014-0225-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005610"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026745"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2011.02.003"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"72","article-title":"High resolution melting for F9 gene mutation analysis in patients with haemophilia B","volume":"17","author":"Salviato R","year":"2019","journal-title":"Blood Transfus"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.6.853"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-13"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.5858\/133.10.1600"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29866","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29866","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T10:43:01Z","timestamp":1692700981000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,11]]},"references-count":23,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/pbc.29866"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29866","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"type":"print","value":"1545-5009"},{"type":"electronic","value":"1545-5017"}],"subject":[],"published":{"date-parts":[[2022,7,11]]},"assertion":[{"value":"2021-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29866"}}