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Clinical Research Programme

H12O - CNIO Haematological Malignancies Clinical Research Unit

Head of Unit:  Joaquín Martínez
Research highlights

During this year, our Group has developed new tools for the diagnosis and surveillance of different haematological diseases using Next Generation Sequencing (NGS):

  • Targeted RNASeq for the identification of Ph-like B-acute lymphoblastic leukaemia (ALL).
  • A novel NGS method for studying BCR-ABL1 protein variants in cDNA from bone marrow and cerebrospinal fluid blast cells from ALL patients.
  • A simplified in-house deep-sequencing method to identify and quantify Minimal Residual Disease in multiple myeloma (MM) patients using NGS of immunoglobulin rearranged genes (FIGURE 1).
  • A specific NGS panel of different genes (NPM1, IDH1, IDH2 or DNMT) for evaluating relapse, drug response and Minimal Residual Disease in myeloid diseases.

On the other hand, new molecular targets have been explored:

  • The new role of PAK 4 in multiple myeloma.
  • The control that hnRNP K exerts on proliferation and differentiation programmes in haematological malignancies such as lymphoma.
  • The activation of the MEK/ERK1/2 pathway during drug resistance in acute myeloid leukaemia.
  • The value of PTCH1 for predicting imatinib response in chronic myeloid leukaemia patients in chronic phase. Finally, a novel treatment strategy using autologous activated and expanded natural killer cells plus anti-myeloma drugs has been developed for multiple myeloma; the strategy has been effective in vitro, ex vivo and in patients with relapsed or refractory myeloma (FIGURE 2).

Moreover, we have demonstrated that the NKG2D receptor, expressed in both natural killer cells and CD8+ T cells, NKG2DNKG2DL could be used as an immunotherapeutic strategy against cancer; NKG2D-4-1BB-CD3z CAR-redirected memory T cells efficiently targeted NKG2DL-expressing osteosarcoma cells in vivo and in vitro.