CRIS: Complete Reconstruction of Immunoglobulin V-D-J Sequences from RNA-seq data

Motivation B-cells display remarkable diversity in producing B-cell receptors through recombination of immunoglobulin V-D-J genes. Somatic hypermutation of immunoglobulin heavy chain variable (IGHV) genes are used as a prognostic marker in B-cell malignancies. Clinically, IGHV mutation status is determined by targeted Sanger sequencing which is a resource intensive and low-throughput procedure. Here we describe a bioinformatic pipeline, CRIS (Complete Reconstruction of Immunoglobulin IGHV-D-J Sequences) that uses RNA sequencing (RNA-seq) datasets to reconstruct IGHV-D-J sequences and determine IGHV somatic hypermutation status. Results CRIS extracts RNA-seq reads aligned to immunoglobulin gene (Ig) loci, performs assembly of Ig-transcripts and aligns the resulting contigs to reference Ig sequences to enumerate and classify somatic hypermutations in the IGHV gene sequence. CRIS improves on existing tools that infer the B-cell receptor (BCR) repertoire from RNA-seq data using a portion IGHV gene segment by de novo assembly. We show that the somatic hypermutation status identified by CRIS using the entire IGHV gene segment is highly concordant with clinical classification in three independent chronic lymphocytic leukemia patient cohorts. Availability The CRIS pipeline is available under the MIT License from https://github.com/Rashedul/CRIS. Supplementary information Supplementary data are available at Bioinformatics Advances online.

Acute myeloid leukemia in a chronic lymphocytic leukemia patient: diagnostic challenge (clinical case).

Chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) coexistence in the same patient has been rarely reported, more frequently due to treatment with chemotherapeutic agents. Blood parameter changes in cancer patients may be interpreted as disease progression or iatrogenic effects related to aggressive treatment, leading to delayed diagnosis. In our article, we call attention to the possibility of AML development in CLL patients and its diagnostic challenge.

Richter’s Transformation as leptomeningeal infiltration in a Chronic Lymphocytic Leukemia patient receiving Venetoclax. Could blood-brain barrier be a disease “sanctuary” during Venetoclax treatment?

We present a unique Richter’s transformation case in CNS with identical to CLL clonal origin in a patient treated with Venetoclax. With our case we make implications on whether Venetoclax penetrates the blood-brain barrier and we address the debating issue of the appropriate Venetoclax dose in case of drug-drug interactions.