Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia.

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT).

Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia.

Purpose: Therapy-related myelodysplastic syndrome and acute leukemias (t-MDS/AL) are a major cause of nonrelapse mortality among pediatric cancer survivors. Although the presence of clonal hematopoiesis (CH) in adult patients at cancer diagnosis has been implicated in t-MDS/AL, there is limited published literature describing t-MDS/AL development in children.

Experimental Design: We performed molecular characterization of 199 serial bone marrow samples from 52 patients treated for high-risk neuroblastoma, including 17 with t-MDS/AL (transformation), 14 with transient cytogenetic abnormalities (transient), and 21 without t-MDS/AL or cytogenetic alterations (neuroblastoma-treated control).

Single-cell mutation analysis of clonal evolution in myeloid malignancies.

Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations.

Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis.

Mutational profiling has demonstrated utility in predicting the likelihood of disease progression in patients with myelofibrosis (MF). However, there is limited data regarding the prognostic utility of genetic profiling in MF patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). We performed high-throughput sequencing of 585 genes on pre-transplant samples from 101 patients with MF who underwent allo-HCT and evaluated the association of mutations and clinical variables with transplantation outcomes.

Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia.

Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation.

and mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation.

The genetic aberrations that drive mixed phenotype acute leukemia (MPAL) remain largely unknown, with the exception of a small subset of MPALs harboring and translocations. We performed clinicopathologic and genetic evaluation of 52 presumptive MPAL cases at Memorial Sloan Kettering Cancer Center. Only 29 out of 52 (56%) cases were confirmed to be bona fide MPAL according to the 2016 World Heath Organization classification.

JAK2/IDH-mutant-driven myeloproliferative neoplasm is sensitive to combined targeted inhibition.

Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617F and mutant IDH1R132H or Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617F Idh2R140Q-mutant MPNs were sensitive to small-molecule inhibition of IDH.

Ageing-induced alterations in lipid/phospholipid profiles of rat brain and liver mitochondria: implications for mitochondrial energy-linked functions.

Effects of ageing on the lipid/phospholipid profile of brain and liver mitochondria from rats were examined. In the brain mitochondria the contents of total phospholipid (TPL) and cholesterol (CHL) increased with simultaneous increase in the TPL/CHL (mole:mole) ratio. The proportion and contents of lysophospholipid (Lyso), sphingomyelin (SPM), phosphatidylinositol (PI), phosphatidylserine (PS) and diphosphatidylglycerol (DPG) components increased, with maximal increases seen for PS and PI; phosphatidylcholine (PC) and phosphatidylethanolamine (PE) components registered decrease.

Thyroid hormone-induced alterations in membrane structure-function relationships: studies on kinetic properties of rat kidney microsomal Na(+),K (+)-ATPase and lipid/phospholipid profiles.

The effects of thyroidectomy (Tx) and subsequent treatment with 3,5,3'-triiodothyronine (T(3)) or combined replacement therapy (T(R)) with T(3 )and thyroxine (T(4)) on the substrate and temperature kinetics properties of Na+,K+-ATPase and lipid/phospholipid makeup of rat kidney microsomes were examined. Enzyme activity was somewhat high in the hypothyroid (Tx) animals and increased significantly following T(3) treatment, while T(R) treatment caused a decrease. In the Tx and T(3) groups enzyme activity resolved in two kinetic components, while in the T(R) group the enzyme showed allosteric behavior up to 0.

Improved method for estimation of inorganic phosphate: implications for its application in enzyme assays.

The conventional method of Fiske and Subba Row for the estimation of inorganic phosphate (Pi) is although rapid, but suffers from the disadvantage that the color is unstable and hence the optical density (OD) measurements have to be carried out within a short time span of 8-12 min. This poses a restriction on the number of samples, which can be handled in a batch. Although, modified procedures involving use of alternate reducing agents/or increasing the concentration of H2SO4 in conventional method have been subsequently developed, but the problem of color stability could not be solved.

Stimulation of oxidative energy metabolism in liver mitochondria from old and young rats by treatment with dehydroepiandrosterone (DHEA). A comparative study.

Effects of treatment with DHEA (0.2 or 1.0 mg/kg body weight for 7 days) on oxidative energy metabolism of rat liver mitochondria from old (18-24 month old) and young (8-10 weeks old) male albino rats belonging to Charles-Foster strain were examined.

Dehydroepiandrosterone treatment alters lipid/phospholipid profiles of rat brain and liver mitochondria.

Stimulation of mitochondrial function following treatment with dehydroepiandrosterone (DHEA) has been demonstrated. Since the activity of several electron transport chain components is dependent on specific lipid/phospholipid components, we examined the effects of DHEA treatment (0.1-2.

Effect of dehydroepiandrosterone (DHEA) treatment on oxidative energy metabolism in rat liver and brain mitochondria. A dose-response study.

Objectives: Effects of treatment with dehydroepiandrosterone (DHEA) on oxidative energy metabolism in rat liver and brain mitochondria were examined.

Design And Methods: Young adult rats were administered DHEA (0.1, 0.

Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy metabolism in the liver mitochondria from developing rats.

Effects of treatment with DHEA (0.2 mg or 1.0 mg / kg body weight for 7 days) on oxidative energy metabolism on liver mitochondria from developing and young adult rats were examined.

Dehydroepiandrosterone (DHEA) treatment stimulates oxidative energy metabolism in the cerebral mitochondria from developing rats.

Effects of treatment with dehydroepiandrosterone (DHEA) (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in cerebral mitochondria from developing and young adult rats were examined.

Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy metabolism in the cerebral mitochondria. A comparative study of effects in old and young adult rats.

The content of the neurosteroids, dehydroepiandrosterone (DHEA) in the brain decreases with aging. Also the oxidative energy metabolism is known to decrease with aging. Hence we examined the effects of treatment with DHEA (0.