Functional Characterization of Organoids Derived From Irreversibly Damaged Liver of Patients With NASH.

Background And Aims: NASH will soon become the leading cause of liver transplantation in the United States and is also associated with increased COVID-19 mortality. Currently, there are no Food and Drug Administration-approved drugs available that slow NASH progression or address NASH liver involvement in COVID-19. Because animal models cannot fully recapitulate human NASH, we hypothesized that stem cells isolated directly from end-stage liver from patients with NASH may address current knowledge gaps in human NASH pathology.

Hairy Cell Leukemia Masquerading as Pancytopenia in Pregnancy.

Thrombocytopenia is one of the most common hematological abnormalities observed during pregnancy, and in rare cases, this may be the first indicator of an underlying hematological malignancy. Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder of which thrombocytopenia is a recurrent presenting feature. A case of pancytopenia presenting in pregnancy is described in which the thrombocytopenia persisted postpartum coincidental with a vesicular, pustular rash characterised as Sweet's syndrome.

Molecular response to imatinib in chronic myeloid leukaemia with a variant e13a3 BCR-ABL1 fusion.

The majority of chronic myeloid leukaemia (CML) patients express either e13a2 or e14a2 BCR-ABL1 transcripts. Variant fusion genes can arise, usually due to alternative splicing of either BCR or ABL1 exons, with molecular monitoring by quantitative PCR (qPCR) in response to tyrosine kinase inhibitor therapy rarely reported in such cases. A case of CML is described in which an e13a3 BCR-ABL1 fusion was characterised.

Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia.

A minority of chronic myeloid leukaemia (CML) patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI) resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy.

BCR-ABL1 kinase domain mutation analysis in an Irish cohort of chronic myeloid leukemia patients.

While tyrosine kinase inhibitor (TKI) therapy is the mainstay of modern management of chronic myeloid leukemia (CML), a significant proportion of CML patients may be refractory or lose their initial response to TKI therapy through a number of cellular and molecular mechanisms of which acquired mutations in the BCR-ABL1 kinase domain (KD) are the most common. BCR-ABL1 KD mutations were prospectively identified in order to inform clinical decisions on subsequent therapy. Direct sequencing of the BCR-ABL1 KD was performed in 85 CML patients that were either TKI refractory or displayed increasing BCR-ABL1 transcript levels by serial monitoring after an initial molecular response.

Chronic Myeloid Leukemia with e19a2 BCR-ABL1 Transcripts and Marked Thrombocytosis: The Role of Molecular Monitoring.

While most patients with chronic myeloid leukemia (CML) express either e13a2 or e14a2 BCR-ABL1 transcripts, a significant minority expresses variant transcripts, of which e19a2 is the most common. Although considered to have a relatively favourable outcome, reported responses to tyrosine kinase inhibitor (TKI) therapy are variable with molecular monitoring in CML patients with e19a2 BCR-ABL1 transcripts rarely reported. A case of e19a2 BCR-ABL1 CML with marked thrombocytosis is described in which the value of molecular monitoring is emphasised during treatment interruptions, dose reductions, and changes.

EGF +61 gene polymorphism and susceptibility to and prognostic markers in cutaneous malignant melanoma.

CMM is the most serious cutaneous malignancy and is increasing in frequency among most Caucasian populations, where the most important risk factor is exposure to UV light. Relatively little is known of the genetic factors that mediate susceptibility to and prognosis in sporadic CMM, although a number of genes have been implicated. A striking association between EGF polymorphism and Breslow thickness of invasive CMM has been reported.

Influence of cytokine gene polymorphisms on the development of prostate cancer.

Polymorphisms in the promoter regions of cytokine genes may influence prostate cancer (PC) development via regulation of the antitumor immune response and/or pathways of tumor angiogenesis. PC patients (247) and 263 controls were genotyped for interleukin (IL)-1beta-511, IL-8-251, IL-10-1082, tumor necrosis factor-alpha-308, and vascular endothelial growth factor (VEGF)-1154 single nucleotide polymorphisms. Patient control comparisons revealed that IL-8 TT and VEGF AA genotypes were decreased in patients compared with controls [23.