Publications by authors named "Amy Carlos"
Article Synopsis
- Acute myeloid leukemia (AML) is a challenging cancer with few treatment options, and the study combines ex vivo drug sensitivity with genomic data from 805 patients to better understand treatment responses.
- This research identifies key features influencing drug sensitivity, particularly focusing on the differentiation state of AML cells, which has implications for how they respond to therapy.
- Notably, the gene PEAR1 emerges as a strong predictor of survival in young AML patients, highlighting its potential role in guiding treatment decisions and future drug development.
Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes.
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- FLT3 mutations are common in AML and lead to a worse prognosis, but crenolanib, a powerful FLT3 inhibitor, shows effectiveness against certain mutations but leads to temporary responses before relapse.
- Research indicates that crenolanib doesn’t create secondary FLT3 mutations, but instead, leads to new mutations in NRAS and IDH2, along with other changes in genes related to epigenetics and transcription in resistant cases.
- Combining crenolanib with other drugs in tests may help overcome resistance and restore its effectiveness.
Article Synopsis
- The Beat AML program analyzed tumor specimens from 562 AML patients to examine complex mutations and drug responses using whole-exome and RNA sequencing.* -
- The study discovered previously undetected mutations and identified how certain drug responses are linked to specific combinations of these mutations.* -
- Findings, including gene expression signatures related to drug responses, are available through the Beat AML data viewer, enabling further research on AML biology.*
Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD.
View Article and Find Full Text PDFAlkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels.
View Article and Find Full Text PDFThe development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development.
View Article and Find Full Text PDFSize and shape are critical determinants of the mechanical properties of skeletal elements and can be anticipated to be highly heritable. Moreover, the genes responsible may be independent of those that regulate bone mineral density (BMD). To begin to identify the heritable determinants of skeletal geometry, we have examined femoral cross-sectional area (FCSA) in male and female mice from two inbred strains of mice with divergent FCSA (C57BL/6 [B6] and DBA/2 [D2]), a large genetically heterogeneous population (n = 964) of B6D2F2 mice and 18 BXD recombinant inbred (RI) strains derived from their F2 cross.
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