Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

Thanks to the unseasonal rain around Diwali, the extended monsoon and growing debt of farmers, non-performing assets (NPAs) among crop loans in Gujarat rose marginally by 3.2% in the third quarter of 2019-20.

Thanks to the unseasonal rain around Diwali, the extended monsoon and growing debt of farmers, non-performing assets (NPAs) among crop loans in Gujarat rose marginally by 3.2% in the third quarter of 2019-20.

Thanks to the unseasonal rain around Diwali, the extended monsoon and growing debt of farmers, non-performing assets (NPAs) among crop loans in Gujarat rose marginally by 3.2% in the third quarter of 2019-20.

In a polarised time, the broadcaster has won listeners by embracing confrontation

In addition, West Bengal will also request the Reserve Bank of India (RBI) to increase the additional credit limit to MSMEs, to 30 per cent from the existing 10 per cent.