AMP case report: Unique patterns of BTK resistance: two independently arising resistance clones in response to covalent BTK inhibitor therapy in CLL/SLL
October 2025—Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a mature B-cell neoplasm composed of small atypical lymphoid cells that often coexpress CD5 and CD23 and are characterized by scant cytoplasm, clumped nuclear chromatin, and indistinct nucleoli. CLL/SLL can involve the peripheral blood, bone marrow, and various lymphoid tissues such as the lymph nodes, tonsils, and spleen, and it may occasionally present in extranodal locations as well.1 Within involved lymph nodes, pale-staining proliferation centers consisting of prolymphocytes or paraimmunoblasts are a characteristic finding in CLL/SLL.