Table_1_An 8-step approach for the systematic development of an evidence-based exercise program for patients undergoing hematopoietic stem cell transplantation.pdf

BackgroundA tailored and reliable intervention program developed based on evidence is necessary for patients with serious health conditions.ObjectiveWe describe the development of an exercise program for HSCT patients based on evidence from a systematic process.MethodsWe developed the exercise program for HSCT patients using eight systematic steps: (1) a literature review, (2) understanding patient characteristics, (3) first expert group discussion, (4) development of the first draft of the exercise program, (5) a pre-test, (6) second expert group discussion, (7) a pilot randomized controlled trial (n=21), and (8) a focus group interview.ResultsThe developed exercise program was unsupervised and consisted of different exercises and intensities according to the patients’ hospital room and health condition. Participants were provided with instructions for the exercise program, exercise videos via smartphone, and prior education sessions. In the pilot trial, the adherence to the exercise program was only 44.7%, however, some changes in physical functioning and body composition favored the exercise group despite the small sample size.ConclusionStrategies to improve adherence to this exercise program and larger sample sizes are needed to adequately test if the developed exercise program may help patients improve physical and hematologic recovery after HSCT. This study may help researchers develop a safe and effective evidence-based exercise program for their intervention studies. Moreover, the developed program may benefit the physical and hematological recovery in patients undergoing HSCT in larger trials, if exercise adherence is improved.Clinical trial registrationhttps://cris.nih.go.kr/cris/search/detailSearch.do?seq=24233&search_page=L, identifier KCT 0008269.</p

Supplementary Figures S1-S5 and Legends from AMPK–ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute Myeloid Leukemia Stem Cells

Supplementary figure S1. Differential sensitivity of human AML LSCs to JQ1. Supplementary figure S2. Relative levels of the autophagy pathway effectors LC3-II, beclin-1, and pULK1 (S555). Supplementary figure S3. Autophagy induction in KG1 and KG1a cells and effects of autophagy inhibition on JQ1-induced apoptosis in LSCs. Supplementary figure S4. JQ1-induced apoptosis through intrinsic apoptosis pathway in JQ1-sensitive LSCs. Supplementary figure S5. Diagram illustrating the potential effects of the BET inhibitor JQ1 in JQ1-resistant LSCs.</p

Table_1_Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights.docx

BackgroundAplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited.MethodsWe retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition.ResultsNine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia.ConclusionThis study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7’s prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression.</p

Supplemental Table 2 from AMPK–ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute Myeloid Leukemia Stem Cells

Patient characteristics according to JQ1 sensitivity in primary acute myeloid leukemia blasts</p

Supplemental Table 1 from AMPK–ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute Myeloid Leukemia Stem Cells

Effects of JQ1 on phenotypes and apoptosis of primary acute myeloid leukemia stem cells from 13 patietns</p

NGS data analysis flow and bioinformatics tools.

NGS data analysis flow and bioinformatics tools.</p

Identification of <i>FLT3</i>- ITD by different NGS algorithms.

Identification of FLT3- ITD by different NGS algorithms.</p

Characterization of mutations.

(A) Mutations classified according to the categories of gene functions. (B) Circos diagram showing co-occurrence and mutual exclusivity of mutations.</p

Additional file 1 of PERK/NRF2 and autophagy form a resistance mechanism against G9a inhibition in leukemia stem cells

Additional file 1: Table S1. Synergistic effects of the G9a and PERK inhibitor on apoptosis of primary acute myeloid LSCs. Figure S1. Effects of treatment with the PERK inhibitor GKS2606414 for 48 h in the presence or absence of 10 μM BIX-01294, on apoptosis. Figure S2. Effect of PERK inhibition on BIX-01294- induced apoptosis in KG1a cells. (A) KG1a cells were treated with 10 μM BIX-01294 in the presence or absence of the PERK inhibitor GSK260641 at 5 μM. After incubation for 48 h, the apoptotic fraction was measured using flow-cytometric analysis. (B) KG1a cells were transfected with PERK siRNA or scrambled siRNA as described in the Materials and Methods and then treated with 10 μM BIX-01294 for 48 h. Figure S3. Effects of treatment for 48 h with the NRF2 inhibitor brusatol in the presence or absence of 10 μM BIX-01294 on apoptosis. Figure S4. Effects of PERK inhibition in the absence or presence of 2 nM bafilomycin A1 on autophagy induction

Genic and exonic CNVs identified.

Genic and exonic CNVs identified.</p