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Journal Articles

Human herpesvirus 6 viremia and encephalitis in CAR T-cell recipients

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Stephanie Teresa Isaac, David C Bishop, Fahad Shaikh, Kenneth P Micklethwaite, David J Gottlieb, Emily Blyth
Journal: Blood
Blood blood.2025029057.
https://doi.org/10.1182/blood.2025029057
Published: 2025
Journal Articles

Impact of immunochemotherapy regimens on outcomes of patients with primary mediastinal B-cell lymphoma in the IELSG37 trial

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Clinical Trials & Observations
Emanuele Zucca, Luca Ceriani, Giovannino Ciccone, Alice Di Rocco, Maria Cristina Pirosa, Iryna Kriachok, Barbara Botto, Monica Balzarotti, MD, Alessandra Tucci, Sara Veronica Usai, Vittorio Ruggero Zilioli, Elsa Pennese, Luca Arcaini, Anna P Dabrowska-Iwanicka, Andrés J.M. Ferreri, Francesco Merli, Wei-Li Zhao, Luigi Rigacci, Claudia Cellini, David Hodgson, Codruta Ionescu, Carla Minoia, Elisa Lucchini, Michele Spina, Alexander Fosså, Andrea Janikova, Kate Cwynarski, N. George Mikhaeel, Mats Jerkeman, Anastasios Stathis, Kelly S Cozens, Nicoletta Ielmini, Iolanda De Martino, Jan Walewski, Marek Trněný, Franco Cavalli, Umberto Ricardi, Peter W. M. Johnson, Andrew J Davies, Maurizio Martelli
Journal: Blood
Blood blood.2025028823.
https://doi.org/10.1182/blood.2025028823
Published: 2025
Includes: Supplemental data
Journal Articles

Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma

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Zhibo Yan, Zhannan Han, Yihui Wang, Maja Beus, Yu Zhang, Alfredo Picado, Carrow I. Wells, Jian Wu, Loren B. Weidenhammer, Karla M. Pires, Elizabeth A. Leibold, Liang Liu, David M. Gooden, Ivan Spasojevic, Erik Soderblom, Yubin Kang, Lawrence H Boise, Timothy M. Willson, Mikhail A. Nikiforov
Journal: Blood
Blood blood.2025029950.
https://doi.org/10.1182/blood.2025029950
Published: 2025
Includes: Supplemental data
Journal Articles

Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN

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Clinical Trials & Observations
Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, Krish Patel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Marie Hughes, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, George Follows, Patricia Walker, Paolo Ghia, Ann Janssens, John C. Byrd, Emmanuelle Ferrant, Alessandra Ferrajoli, William G. Wierda, Catherine Wangui Wachira, Batul T. Suterwala, Paulo Miranda, Veerendra Munugalavadla, Chuan-Chuan Wun, Jennifer A. Woyach
Journal: Blood
Blood (2025) 146 (11): 1276–1285.
https://doi.org/10.1182/blood.2024024476
Published: 2025
Includes: Supplemental data
Journal Articles

Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism

Open Access
Yaqiu Sang, Marzia Menegatti, Jennifer A. Brody, Kerri L. Wiggins, Brian C. Cooley, Katheryn N. Kapfer, Kadri Kangro, Bas de Laat, Flora Peyvandi, Matthew J. Flick, Nicholas L. Smith, Amy D. Shapiro, Alisa S. Wolberg
Journal: Blood
Blood (2025) 146 (11): 1346–1358.
https://doi.org/10.1182/blood.2025028680
Published: 2025
Includes: Supplemental data
Journal Articles

Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer

Open Access
Bernd B. Zeisig, Chiou-Tsun Tsai, Clemence Virely, Tsz Kan Fung, Ali Tuğrul Akin, Estelle Troadec, Bo Jiao, I. Richard Thompson, Priscilla Nga Ieng Lau, Nanjun Li, Andriani Charalambous, Larissa Bomfim, Jennifer Lynch, Athina Georgiou, Robbert Hoogeboom, Claire Lynn, Si-Yi Zhang, Piers E. M. Patten, Cynthia L. Fisher, Anna Schuh, Seishi Ogawa, Ghulam Mufti, Mohammad M. Karimi, Chi Wai Eric So
Journal: Blood
Blood (2025) 146 (11): 1314–1330.
https://doi.org/10.1182/blood.2025028560
Published: 2025
Includes: Supplemental data
Images
Investigator-assessed PFS overall. ∗HR based on stratified Cox proportional hazards model; †P value based on stratified log-rank test. ‡HR based on unstratified Cox proportional hazards model; §P value based on unstratified log-rank test. A, acalabrutinib; Clb, chlorambucil; O, obinutuzumab.

Investigator-assessed PFS overall. ∗HR based on stratified Cox proportiona...

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in Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN > Blood
Published: 2025
Figure 1. Investigator-assessed PFS overall. ∗HR based on stratified Cox proportional hazards model; † P value based on stratified log-rank test. ‡HR based on unstratified Cox proportional hazards model; § P value based on unstratified log-rank test. A, acalabrutinib; Clb, chlorambucil; O, obi... More about this image found in Investigator-assessed PFS overall. ∗HR based on stratified Cox proportiona...
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ORRs∗ and CR/CRi rates over follow-up period in patients treated with A-O or A monotherapy. ∗Best investigator-assessed response could be determined at any scheduled, per-protocol follow-up visit. ORR is defined as achieving CR, CRi, nPR, or PR per the investigator per International Workshop on CLL 2008 criteria21 at or before initiation of subsequent anticancer therapy. ORR does not include partial response except for lymphocytes. A, acalabrutinib; nPR, nodular partial response; O, obinutuzumab; PR, partial response.

ORRs∗ and CR/CRi rates over follow-up period in patients treated with A-O o...

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in Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN > Blood
Published: 2025
Figure 2. ORRs∗ and CR/CRi rates over follow-up period in patients treated with A-O or A monotherapy. ∗Best investigator-assessed response could be determined at any scheduled, per-protocol follow-up visit. ORR is defined as achieving CR, CRi, nPR, or PR per the investigator per International Wo... More about this image found in ORRs∗ and CR/CRi rates over follow-up period in patients treated with A-O o...
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OS in patients overall. ∗HR based on stratified Cox proportional hazards model; †P value based on stratified log-rank test. ‡HR based on unstratified Cox proportional hazards model; §P value based on unstratified log-rank test. Clb, chlorambucil.

OS in patients overall. ∗HR based on stratified Cox proportional hazards m...

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in Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN > Blood
Published: 2025
Figure 3. OS in patients overall. ∗HR based on stratified Cox proportional hazards model; † P value based on stratified log-rank test. ‡HR based on unstratified Cox proportional hazards model; § P value based on unstratified log-rank test. Clb, chlorambucil. More about this image found in OS in patients overall. ∗HR based on stratified Cox proportional hazards m...
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Genetic loss of plasminogen does not increase venous thrombus formation or change cellular or fibrin(ogen) deposition. (A) PA curves in PPP from Plg+/+, Plg+/−, Plg–/– mice; representative of N = 5 to 9 mice per genotype. (B-C) The mass of venous thrombi harvested from Plg+/+, Plg+/−, Plg–/– mice 24 or 6 hours after IVC ligation. (D) Representative images of 6-hour thrombi probed to identify nuclei/DNA (DAPI [4′,6-diamidino-2-phenylindole], blue), platelets (anti-CD41, red), or fibrin(ogen) (polyclonal antibody, green). Scale bars indicate 100 μm. Methods for acquiring and processing images are provided in the supplemental Materials. (E) Quantification of nuclei, platelets, and fibrin(ogen) in 6-hour thrombi. Graphs show mean ± standard deviation or median ± interquartile range, as appropriate; each dot indicates a separate mouse. Groups were compared by ordinary 1-way analysis of variance with Šidák multiple comparisons test or Kruskal-Wallis test with Dunn multiple comparisons test for normally and nonnormally distributed data, as appropriate; no groups were significantly different.

Genetic loss of plasminogen does not increase venous thrombus formation or ...

Open Access
in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 1. Genetic loss of plasminogen does not increase venous thrombus formation or change cellular or fibrin(ogen) deposition. (A) PA curves in PPP from Plg +/+ , Plg +/− , Plg –/– mice; representative of N = 5 to 9 mice per genotype. (B-C) The mass of venous thrombi harvested fro... More about this image found in Genetic loss of plasminogen does not increase venous thrombus formation or ...
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TXA inhibits plasminogen activation and/or PA in vitro and ex vivo. (A) Mouse normal pooled plasma was diluted 1:6 in HEPES buffer with TXA (concentrations indicated in the legend) and then clotted in the presence of tissue factor, phospholipids, recombinant tissue plasminogen activator, and CaCl2. Fluorescence was monitored over time. Representative curves from 3 replicates are shown. (B-G) Saline or TXA (600 mg/kg) was injected intraperitoneally into wild-type mice. Blood was collected from the inferior vena cava into 3.2% sodium citrate (10% vol/vol, final) and used to prepare plasma for PA measurements. Representative curves of mice treated with (B) saline or (C) TXA for each time point. (D-G) Parameters: (D) lag time, (E) time to peak, (F) velocity, and (G) peak. Saline and TXA treatments are indicated in black and red, respectively. Dots and error bars show mean ± standard error of the mean, N = 4 to 9 individual mice per time point. Groups were compared by ordinary 1-way analysis of variance with the Šidák or the Holm-Šidák multiple comparisons test; ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001 for comparisons at each time point. TtPeak, time to peak.

TXA inhibits plasminogen activation and/or PA in vitro and ex vivo. (A) Mo...

Open Access
in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 2. TXA inhibits plasminogen activation and/or PA in vitro and ex vivo. (A) Mouse normal pooled plasma was diluted 1:6 in HEPES buffer with TXA (concentrations indicated in the legend) and then clotted in the presence of tissue factor, phospholipids, recombinant tissue plasminogen activato... More about this image found in TXA inhibits plasminogen activation and/or PA in vitro and ex vivo. (A) Mo...
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Pharmacologic inhibition of fibrinolysis does not increase venous thrombus mass or change cellular or fibrin(ogen) deposition in thrombi. Saline or TXA (600 mg/kg)–treated mice were subjected to IVC ligation. (A-B) The mass of venous thrombi harvested from wild-type mice after (A) 24 or (B) 6 hours. (C) Representative images of 24-hour thrombus sections probed to identify nuclei/DNA (DAPI [4′,6-diamidino-2-phenylindole], blue), platelets (anti-CD41, red), or fibrin(ogen) (polyclonal antibody, green). Scale bars indicate 100 μm. Methods for acquiring and processing images are provided in the supplemental Materials. (D) Quantification of nuclei, platelets, and fibrin(ogen) in 24-hour thrombi. (E) Representative images of 6-hour thrombus sections probed to identify nuclei/DNA (DAPI, blue), platelets (anti-CD41, red), or fibrin(ogen) (polyclonal antibody, green). Scale bars indicate 100 μm. (F) Quantification of nuclei, platelets, and fibrin(ogen) in 6-hour thrombi. Graphs show mean ± standard deviation or median ± interquartile range, as appropriate. Groups were compared by the unpaired t-test or the Mann-Whitney test for normally and nonnormally distributed data, as appropriate; no groups were significantly different.

Pharmacologic inhibition of fibrinolysis does not increase venous thrombus ...

Open Access
in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 3. Pharmacologic inhibition of fibrinolysis does not increase venous thrombus mass or change cellular or fibrin(ogen) deposition in thrombi. Saline or TXA (600 mg/kg)–treated mice were subjected to IVC ligation. (A-B) The mass of venous thrombi harvested from wild-type mice after (A) 24 o... More about this image found in Pharmacologic inhibition of fibrinolysis does not increase venous thrombus ...
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IVC ligation prolongs TXA circulation in plasma. (A-B) PA in plasma from wild-type mice treated with saline (black) or TXA (red) and 24 or 6 hours of IVC ligation; each line shows a separate mouse. (C) TXA concentration and (D) correlation of TXA concentration with plasmin peak in plasma from wild-type mice treated with saline or TXA and subjected to IVC ligation. (E) FDPs in plasma from wild-type mice treated with saline or TXA and subjected to IVC ligation. Graphs show mean ± standard deviation or median ± interquartile range, as appropriate; each dot indicates a separate mouse. Groups were compared by the ordinary 1-way analysis of variance with the Šidák multiple comparisons test or the Kruskal-Wallis test with the Dunn multiple comparisons test for normally and nonnormally distributed data, as appropriate; ∗∗P < .01, ∗∗∗P < .001.

IVC ligation prolongs TXA circulation in plasma. (A-B) PA in plasma from w...

Open Access
in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 4. IVC ligation prolongs TXA circulation in plasma. (A-B) PA in plasma from wild-type mice treated with saline (black) or TXA (red) and 24 or 6 hours of IVC ligation; each line shows a separate mouse. (C) TXA concentration and (D) correlation of TXA concentration with plasmin peak in plas... More about this image found in IVC ligation prolongs TXA circulation in plasma. (A-B) PA in plasma from w...
Images
Quantile-quantile plot of observed vs expected P values from the genome-wide association analysis for positive controls, negative controls, and hypothesis-based PA pathway genes and VTE incidence. Expected vs observed –log10 of P values. Data points showing negative control genes (gray) and PA pathway genes (red) overlap. The minimum P value for F5 (rs6025, FV Leiden, P < 1.00E-300) is not shown in the plot.

Quantile-quantile plot of observed vs expected P values from the genome-w...

Open Access
in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 5. Quantile-quantile plot of observed vs expected P values from the genome-wide association analysis for positive controls, negative controls, and hypothesis-based PA pathway genes and VTE incidence. Expected vs observed –log10 of P values. Data points showing negative control genes (... More about this image found in Quantile-quantile plot of observed vs expected P values from the genome-w...
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Adjusted hazard ratios for the association of PA pathway-related proteins with VTE incidence. All models were adjusted for sex, race, and age at blood draw. &For (soluble) uPAR, the model was also adjusted for C-reactive protein. $For PAI-1, the model was also adjusted for body mass index. ˆFor tPA, the model was also adjusted for body mass index and PAI-1. Red symbols indicate significant associations (P < .007). α2AP, α2-antiplasmin; CI, confidence interval.

Adjusted hazard ratios for the association of PA pathway-related proteins w...

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in Plasminogen activation and plasmin activity are not necessary to prevent venous thrombosis/thromboembolism > Blood
Published: 2025
Figure 6. Adjusted hazard ratios for the association of PA pathway-related proteins with VTE incidence. All models were adjusted for sex, race, and age at blood draw. & For (soluble) uPAR, the model was also adjusted for C-reactive protein. $ For PAI-1, the model was also adjusted for body... More about this image found in Adjusted hazard ratios for the association of PA pathway-related proteins w...
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dKO of Asxl1 and Ezh2 leads to the development of myelodysplastic disorders with high penetrance. (A) Schematic diagram of the primary transplantation experiment. (B) Percentages of LSK, myeloid progenitors (Lin–c-kit+Sca1–), and their subpopulations: LT-HSCs (CD48–CD150+), ST-HSCs (CD48–CD150–), MPP3/4 (CD48+CD150–), MPP2 (CD48+CD150+), GMP (CD16/32+CD34+), CMP (CD16/32–CD34+), and MEP (CD16/32–CD34–) in BM from indicated mutant mice 4 weeks after tamoxifen treatment are shown. WT, n = 6; all other groups, n = 5. (C) Absolute cell counts of CD45.2+ LSK and myeloid progenitors in BM are shown. WT, n = 6; all other groups, n = 5. (D) Kaplan-Meier survival curves of WT (n = 8), Asxl1–/– (n = 6), Ezh2–/– (n = 8), and Asxl1–/–Ezh2–/– (n = 13) mice in primary transplantation. (E) Representative images of May-Grunwald Giemsa staining of BM from indicated mice and PB smears from Asxl1–/–Ezh2–/– mice. Myeloid dysplastic cells such as monolobated megalokaryocytes (1), pseudo–Pelger-Huët anomalies (2), binucleated megakaryocytes (3), Howell Jolly bodies (4), and giant platelets (5) were found in the mice with myelodysplasia. (F) Blood counts of WT, Asxl1–/–, Ezh2–/–, and Asxl1–/–Ezh2–/– mice with indicated disease phenotypes in primary transplantation. Statistical analysis is shown for the indicated groups, unless otherwise stated. (G) The percentages of hematopoietic cells Bl/Pro, My/Met, band cells, and Ne in granulopoiesis from WT and KO mice with MDS/MPN phenotypes. WT and Asxl1–/–, n = 3 each; EZH2–/–, n = 2; Asxl1–/–Ezh2–/–, n = 5. (H) Spleen weights (left) and representative photos of spleens (right) for the indicated genotypes and disease phenotypes. WT, n = 5; Asxl1–/–, n = 6; Ezh2–/–, n = 8; Asxl1–/–Ezh2–/–, n = 12. Plots show mean ± standard error of the mean (SEM). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001, unpaired t test. Bl/Pro, blasts/promyelocytes; CMP, common myeloid progenitor; ET, essential thrombocythemia; GMP, granulocyte-monocyte progenitor; Hgb, hemoglobin; Lin–, lineage negative; LT-HSC, long-term HSC; MEP, megakaryocyte–erythroid progenitor; MPP3/4, multipotent progenitor 3/4; My/Met, myelocytes/metamyelocytes; Ne, neutrophils; Plt, platelets; PV, polycythemia vera; RBC, red blood cells; ST-HSC, short-term HSC; WBC, white blood cells.

dKO of Asxl1 and Ezh2 leads to the development of myelodysplastic disorders...

Open Access
in Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer > Blood
Published: 2025
Figure 1. dKO of Asxl1 and Ezh2 leads to the development of myelodysplastic disorders with high penetrance. (A) Schematic diagram of the primary transplantation experiment. (B) Percentages of LSK, myeloid progenitors (Lin – c-kit + Sca1 – ), and their subpopulations: LT-HSCs (CD48 – CD150 + ), S... More about this image found in dKO of Asxl1 and Ezh2 leads to the development of myelodysplastic disorders...
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Serial transplantation of Asxl1–/–Ezh2–/– cells lead to aggressive CLL. (A) The percentage of B220–/low B cells in CD45.2+ splenocytes from mice that received primary transplant with indicated genotypes and disease phenotypes are shown. Asxl1–/–Ezh2–/– (MDS/MPN, LPD), n = 4; all other sample types, n = 3. (B) The heat map shows normalized read counts of 124 IGHV in the BM from mice that received primary transplant with the indicated genotype. The monoclones with substantial expansion are pointed out. (C) Kaplan-Meier survival curves of secondary transplants; mice were transplanted with BM cells harvested from mice that received primary transplant with the indicated genotypes and disease phenotypes. WT, n = 5; Asxl1–/–, n = 5; Ezh2–/– (MDS/MPN, LPD), n = 10; Asxl1–/–Ezh2–/– (MDS/MPN, LPD), n = 13; Asxl1–/–Ezh2–/– (MDS/MPN), n = 3 mice. Representative images of the SPs are shown. (D) Engraftments of total donor cells (CD45.2+) and the ratios of myeloid and lymphoid populations in the donor population from the BM and SP (as indicated) of WT (BM, n = 4; SP, n = 3) and Asxl1–/–Ezh2–/– dKO secondary CLL (n = 6) mice. (E) May-Grunwald Giesma staining of BM (original magnification x40) cells and PB (x40) smears, and hematoxylin and eosin staining of the SP (x20) and LV (x10) of Asxl1–/–Ezh2-/- dKO secondary CLL mice. (F) Representative flow cytometry profiling of CLL cells in BM from Asxl1–/–Ezh2–/– dKO secondary CLL mice. (G) The dot plot represents the percentages of CD19+CD5+ cells in donor cells from BM (n = 3) and SPs (n = 2) from Asxl1–/–Ezh2–/– dKO secondary CLL mice compared with WT BM (n = 3). (H) Proportions of κ/λ light chains in CD19+ donor splenocytes isolated from Asxl1–/–Ezh2–/– dKO secondary CLL or WT mice as indicated. (I) Kaplan-Meier survival curves of tertiary transplants. Mice were transplanted with BM cells and splenocytes from a secondary Asxl1–/–Ezh2–/– CLL mouse or splenocytes from a secondary TCL1 CLL mouse. Plots show mean ± SEM. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001, unpaired t test. A/E, Asxl1-/-Ezh2-/-; LV, liver; SP, spleen; TCL1, T-cell leukemia/lymphoma 1A oncogene.

Serial transplantation of Asxl1 –/– Ezh2 –/– cells lead to aggressive CLL....

Open Access
in Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer > Blood
Published: 2025
Figure 2. Serial transplantation of Asxl1 –/– Ezh2 –/– cells lead to aggressive CLL. (A) The percentage of B220 –/low B cells in CD45.2 + splenocytes from mice that received primary transplant with indicated genotypes and disease phenotypes are shown. Asxl1 –/– Ezh2 –/– (MDS/MPN, LPD), n = 4... More about this image found in Serial transplantation of Asxl1 –/– Ezh2 –/– cells lead to aggressive CLL....
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Figure 3.

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Open Access
in Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer > Blood
Published: 2025
Figure 3. More about this image found in Untitled image
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Open Access
in Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer > Blood
Published: 2025
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DNA repair pathways are uniquely active in ERV re-expressing Asxl1–/–Ezh2–/– dKO cells. (A) Venn diagram showing the overlaps of differentially expressed genes (adjusted P < .05) identified in the data set derived from the BM of mice that received primary transplant with the indicated genotype, by comparing each genotype, Asxl1–/–, Ezh2–/– MDS/MPN LPD, and Asxl1–/–Ezh2–/– dKO MDS/MPN LPD mice with WT. (B) The bar charts show example pathways identified in gene ontology analysis comparing Asxl1–/– vs WT or Ezh2–/– vs WT (top) and Asxl1–/–Ezh2–/– dKO vs WT (bottom). (C) Example GSEA plots for the indicated pathways in the indicated comparisons are shown. (D-G) Gene set variant analysis (GSVA) for the indicated samples was performed and mean scores for Reactome and Hallmark DNA repair gene sets for each genotype are plotted in the heat map. Different RNA-seq data sets were used for the analysis, c-kit+ 5 days after start of in vivo deletion (D), c-kit+ 3 months after in vivo deletion (E), BM (F), and CD19+ splenocytes (G). (H) Dot plots show selected results for Kyoto Encyclopedia of Genes and Genomes pathway analysis using genes expressed in CLL in the indicated comparisons (WT vs tertiary Asxl1–/–Ezh2–/– dKO CLL or WT vs tertiary TCL1 CLL). DNA repair pathways are marked with a star. (I) GSEA results for selected DNA repair gene sets for tertiary Asxl1–/–Ezh2–/– dKO CLL vs tertiary TCL1 CLL are shown. (J) Dot plot showing the differential expression of the indicated TE families in BM RNA-seq data from mice that received primary transplant, comparing KO vs WT and dKO vs single KO as indicated. (K) Similar dot plot as shown in panel J but using CD19+ splenocyte RNA-seq data from mice that received primary transplant. (L) Dot plot showing the differential expression of the indicated TE families using CD19+ splenocytes isolated from tertiary Asxl1–/–Ezh2–/– dKO CLL, tertiary TCL1 CLL mice, or WT mice as control. (M) The plot shows the integration of differential expression analysis using CD19+ RNA-seq data and quantitative H3K27me3 and H3K27ac CUT&RUN data for the indicated TE families in CD19+ splenocytes isolated from tertiary Asxl1–/–Ezh2–/– dKO CLL mice or WT mice as control. (N) The genome tracks show examples of differentially expressed individual ERVs (RNA-seq top 2 tracks) and the H3K27me3 and H3K27ac levels in WT and tertiary Asxl1–/–Ezh2–/– dKO CLL mice as indicated. The last 2 tracks show control IgG enrichment. H3K27ac, H3K27 acetylation; H3K27me3, H3K27 trimethylation; IgG, immunoglobulin G.

DNA repair pathways are uniquely active in ERV re-expressing Asxl1 –/– Ezh2...

Open Access
in Transposable elements as novel therapeutic targets for PARPi-induced synthetic lethality in PcG-mutated blood cancer > Blood
Published: 2025
DNA repair pathways are uniquely active in ERV re-expressing Asxl1 –/– Ezh2 –/– dKO cells. (A) Venn diagram showing the overlaps of differentially expressed genes (adjusted P < .05) identified in the data set derived from the BM of mice that received primary transplant with the indicated geno... More about this image found in DNA repair pathways are uniquely active in ERV re-expressing Asxl1 –/– Ezh2...