Chronic lymphocytic leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer.

A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion

“…BCR signaling is highly active in CLL cells, but variation in the activity of this pathway has been identified (Burger and Wiestner, 2018; Kipps et al, 2017). Our proteome observations led us to investigate the basal and induced BCR signaling activity in the different mice lines.…”

Diagnosis and classification of hematologic malignancies on the basis of genetics

“…68 For these reasons, analysis of TP53 and IGHV mutational status has recently been incorporated into a new International Prognostic Index for treatment-naive CLL patients (the CLL-International Prognostic Index). 69 Finally, sequencing of .100 whole genomes 70,71 and .500 whole exomes [71][72][73][74] of CLL patients has now revealed recurrent somatic mutations, including those potentially associated with adverse outcome such as mutations in NOTCH1, SF3B1, and ATM (discussed in several excellent recent reviews: Rodríguez et al, 75 Kipps et al, 76 Guièze and Wu, 77 and Lazarian et al 78 ; Table 3). With the exception of TP53 alterations, however, detection of other mutations in CLL is not currently included in routine clinical practice in CLL as their prognostic relevance is not clear.…”

In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI

“…1 The clinical course of the disease is quite heterogeneous with some patients living for years with asymptomatic disease and others experiencing early progression and requiring therapeutic interventions.…”