Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4 T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively.

Changes associated with the development of resistance to imatinib (STI571) in two leukemia cell lines expressing p210 Bcr/Abl protein.

Background: Although various mechanisms have been recognized as being associated with the development of resistance to imatinib mesylate in vitro and in clinical situations, their relative significance and contributions remain poorly understood, as is the sequence of events leading to the selection of the resistant phenotype. Experimental in vitro systems involving well defined cell lines and conditions can be used to some advantage to answer specific questions and to develop in vitro models of imatinib resistance that would reflect its potential heterogeneity.

Methods: Two cell lines, KBM5 and KBM7, which expressed p210 Bcr/Abl and which differed in their inherent sensitivity to imatinib, the number of copies of the BCR/ABL fusion gene, and the activation of apoptotic pathways, were grown in vitro in the presence of increasing concentrations of imatinib.

The proteasome inhibitor PS-341 inhibits growth and induces apoptosis in Bcr/Abl-positive cell lines sensitive and resistant to imatinib mesylate.

Background And Objectives: Imatinib mesylate (IM) is the choice treatment for Bcr/Abl-positive malignancies. Emergence of resistance to IM warrants the exploration of novel well-tolerated anticancer agents. We intended to evaluate the effect of PS-341 on proliferation, survival, and cellular events in Bcr/Abl-positive cells sensitive and resistant to IM, and to investigate the effect of PS-341 and IM in conjunction.

Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS).

Prospective analysis of the importance of the plasma levels of beta-2 microglobulin (B2M) in 553 patients with myelodysplastic syndrome (MDS) found that B2M is an independent prognostic variable for survival with weighted significance second only to the karyotype. The incorporation of the B2M covariate into risk assessment of MDS patients added significantly to the power of the IPSS to stratify MDS patients into risk categories. Our results further document that the 2 objectively measured covariates that display the highest power to predict survival, that is, karyotype and B2M, can alone be used for risk stratification.

Mutation in the ATP-binding pocket of the ABL kinase domain in an STI571-resistant BCR/ABL-positive cell line.

The major mechanism of action of STI571 is a competitive interference with the ATP-binding site of the Bcr/Abl tyrosine kinase. In the BCR/ABL-positive cell line KBM5, we studied cellular events associated with the in vitro acquisition of resistance to STI571. The emergence of the STI571-resistant phenotype was accompanied by only a marginal increase in the number of copies of the BCR/ABL gene and its level of expression.