Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient
Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient
For Taiwanese patients 50 to 64 years of age, the annual stroke risk was 1.78%, which may exceed the threshold for OAC use for stroke prevention. The annual risk of ischemic stroke for AF patients <50 years of age was 0.53%, which was truly low-risk, and OACs could be omitted. Whether resetting the age threshold to 50 years could refine current clinical risk stratification for Asian AF patients deserves further study.
Driver somatic mutations for aldosterone excess have been found in ≈90% of aldosterone-producing adenomas (APAs) using an aldosterone synthase (CYP11B2)-guided sequencing approach. In the present study, we identified a novel somatic
CACNA1H
mutation (c.T4289C, p.I1430T) in an APA without any currently known aldosterone-driver mutations using CYP11B2 immunohistochemistry-guided whole exome sequencing. The
CACNA1H
gene encodes a voltage-dependent T-type calcium channel alpha-1H subunit. Germline variants in this gene are known as a cause of familial hyperaldosteronism IV. Targeted next-generation sequencing detected identical
CACNA1H
variants in 2 additional APAs in a cohort of the University of Michigan, resulting in a prevalence of 4% (3/75) in APAs. We tested the functional effect of the variant on adrenal cell aldosterone production and
CYP11B2
mRNA expression using the human adrenocortical HAC15 cell line with a doxycycline-inducible
CACNA1H
I1430T
mutation. Doxycycline treatment increased
CYP11B2
mRNA levels as well as aldosterone production, supporting a pathological role of the
CACNA1H
p.I1430T mutation on the development of primary aldosteronism. In conclusion, somatic
CACNA1H
mutation is a genetic cause of APAs. Although the prevalence of this mutation is low, this study will provide better understanding of molecular mechanism of inappropriate aldosterone production in APAs.
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