Optimizing Clinical Trial Eligibility Design Using Natural Language Processing Models and Real-World Data: Algorithm Development and Validation.

Background: Clinical trials are vital for developing new therapies but can also delay drug development. Efficient trial data management, optimized trial protocol, and accurate patient identification are critical for reducing trial timelines. Natural language processing (NLP) has the potential to achieve these objectives.

PAK Kinase Inhibition Has Therapeutic Activity in Novel Preclinical Models of Adult T-Cell Leukemia/Lymphoma.

Purpose: To evaluate therapeutic activity of PAK inhibition in ATLL and to characterize the role of PAK isoforms in cell proliferation, survival, and adhesion of ATLL cells in preclinical models.

Experimental Design: Frequency and prognostic impact of amplification were evaluated in an ATLL cohort of 370 cases. Novel long-term cultures and xenograft models were developed using primary ATLL cells from North American patients.

North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies.

Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic in Japanese, Caribbean, and Latin American populations. Most North American ATLL patients are of Caribbean descent and are characterized by high rates of chemo-refractory disease and worse prognosis compared with Japanese ATLL. To determine genomic differences between these 2 cohorts, we performed targeted exon sequencing on 30 North American ATLL patients and compared the results with the Japanese ATLL cases.

An oxidative stress-based mechanism of doxorubicin cytotoxicity suggests new therapeutic strategies in ABC-DLBCL.

Diffuse large B-cell lymphomas (DLBCLs) contain 2 major molecular subtypes; namely, the germinal center B-cell-like (GCB) and the activated B-cell-like (ABC) DLBCLs. It is well documented that ABC-DLBCL cases have a significantly poorer survival response than GCB-DLBCLs in both the CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and the rituximab (R)-CHOP eras. However, the underlying cause of this subtype disparity is poorly understood.

A Bach2 link between pre-B cell receptor checkpoint and pre-B cell ALL.

Bach2 is a transcription factor required for affinity maturation of B cells. A recent study reveals, quite unexpectedly, that Bach2 also plays a key role in the pre-B cell receptor checkpoint and functions as a tumor suppressor in pre-B cell acute lymphocytic leukemia.

Expression of IMP1 enhances production of murine leukemia virus vector by facilitating viral genomic RNA packaging.

Murine leukemia virus (MLV)-based retroviral vector is widely used for gene transfer. Efficient packaging of the genomic RNA is critical for production of high-titer virus. Here, we report that expression of the insulin-like growth factor II mRNA binding protein 1 (IMP1) enhanced the production of infectious MLV vector.