Page 123 - Haematologica - Vol. 105 n. 6 - June 2020

DNA methylation in T-ALL
Additionally, MS-MLPA has the advantage of requiring lit- tle DNA and does not require DNA bisulfite conversion or immunoprecipitation. MS-MLPA is readily compatible with clinical routine and could enhance prognostication and precision medicine.
However, array analysis or methylation analysis at the whole genome level would be relevant in T-ALL to gain information and investigate how aberrant methylation patterns are involved in leukemogenesis. We have observed that aberrant methylation profiles were mostly associated with the driver oncogene involved. In particu- lar, a hypoM subgroup with unfavorable outcome is main- ly enriched in SIL-TAL1+ cases and also in cases negative for the main oncogenes TLX1, TLX3, SIL-TAL1 and HOXA. Deciphering the molecular mechanism of aber- rant methylation and the relationship with driver onco- genes could identify new deregulated pathways for adapt- ed-therapy.
Acknowledgments
We thank all French, Swiss and Belgian participants, clini- cians, biologists and clinical research assistants, in the LALA-94 and GRAALL 2003-2005 trials, for collecting and providing data and samples.
Funding
MeDIP experiments were supported by the INCA-project PAIR-Lymphomes. Work in SS laboratory was supported by Ligue contre le Cancer (Equipe labellisée). Work in the Necker hematology department and SS laboratory was supported by grants from ITMO (Institut Thématique Multi-Organisme) épigénétique et cancer. The GRAALL was supported by grants P0200701 and P030425/AOM03081 from Le Programme Hospitalier de Recherche Clinique, Ministère de l’Emploi et de la Solidarité, France and the Swiss Federal Government in Switzerland. AT was supported by a grant from the French pro- gram CARPEM (CAncer Research for PErsonalized Medicine).
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