Journal of Leukemia
Open Access

Department of Hematology and Translational Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy

Publications

• Mini Review   
  Treatment Refractoriness to Pathway Inhibitors in Chronic Lymphocytic Leukemia
  Author(s): Nawar Maher*, Samir Mouhssine and Gianluca Gaidano
  
  Therapeutic options for Chronic Lymphocytic Leukemia (CLL) rely on pathway inhibitors targeting Bruton Tyrosine Kinase (BTK) or B Cell Lymphoma 2 (BCL2), while the use of Chemo Immunotherapy (CIT) is limited to contexts where pathway inhibitors are not available or accessible. Biomarkers of treatment refractoriness to CIT include the unmutated status of immunoglobulin heavy chain variable genes and genetic alterations of TP53, NOTCH1, and BIRC3. Acquired mutations of BTK and PLCG2 genes represent the most common resistance mechanisms in patients receiving covalent BTK inhibitors (BTKi)-based therapy. The most frequent BTK mutations are C481S and C481R and impair binding of the drug to its target. Mutations of PLCG2 promote B cell receptor signaling despite BTK inhibition. Recently, several BTK point muta.. View More»
  DOI: 10.35248/2329-6917.23.11.348

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