GATA1 mutation analysis and molecular landscape characterization in acute myeloid leukemia with trisomy 21 in pediatric patients

International Journal of Laboratory Hematology - Tập 43 Số 4 - Trang 713-723 - 2021
А. В. Панферова1, Marina Gaskova1, Eugenyi Nikitin1, Pavel Baryshev1, Natalia Timofeeva1, Anna Kazakova1, V. E. Matveev1, Ekaterina Mikhailova1, А. М. Попов1, И. И. Калинина1, Lili Hachatrian1, Aleksey Maschan1, Michael Maschan1, Galina Novichkova1, Yulia Olshanskaya1
1Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia

Tóm tắt

AbstractIntroductionAccurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions.MethodsThe DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high‐throughput sequencing (HTS).ResultsAcquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively.ConclusionsThe GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway‐activating mutations may represent an extra option of targeted therapy with kinase inhibitors.

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International Journal of Laboratory Hematology

Tập 43 Số 4

713-723

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