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Journal Articles

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

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Clinical Trials & Observations
Stephanie T. Isaac, David C. Bishop, Fahad Shaikh, Kenneth Micklethwaite, David J. Gottlieb, Emily Blyth
Journal: Blood
Blood (2025) 146 (25): 3124–3128.
https://doi.org/10.1182/blood.2025029057
Published: 2025
Journal Articles

Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial

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CME Clinical Trials & Observations
Françoise Kraeber-Bodéré, Bastien Jamet, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clément Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Philippe Moreau, Thomas Carlier, Cyrille Touzeau
Journal: Blood
Blood (2025) 146 (25): 3050–3058.
https://doi.org/10.1182/blood.2025030084
Published: 2025
Includes: Supplemental data
Journal Articles

MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia

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Brief Report
Dorien Pastoors, Marije Havermans, Roger Mulet-Lazaro, Leonie Smeenk, Sophie Ottema, Claudia Erpelinck-Verschueren, Stanley van Herk, Maikel Anthonissen, Tim Grob, Shruthi Subramanian, Julie A. I. Thoms, John E. Pimanda, Bas J. Wouters, Berna Beverloo, Torsten Haferlach, Claudia Haferlach, Johannes Zuber, Eric Bindels, Ruud Delwel
Journal: Blood
Blood (2025) 146 (25): 3098–3105.
https://doi.org/10.1182/blood.2025028914
Published: 2025
Includes: Supplemental data
Journal Articles

LEF1 intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL

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Clinical Trials & Observations
Manon Delafoy, Mickaël F. Bonnet, Etienne Lengliné, Agata Cieslak, Aurore Touzart, Estelle Balducci, Mathieu Simonin, Véronique Lhéritier, Marie Emilie Dourthe, Benoît Heid-Picard, Sylvain Latour, Hervé Dombret, Philippe Rousselot, André Baruchel, Nicolas Boissel, Guillaume P. Andrieu, Vahid Asnafi
Journal: Blood
Blood (2025) 146 (25): 3036–3049.
https://doi.org/10.1182/blood.2025030161
Published: 2025
Includes: Supplemental data
Journal Articles

Genomic landscape of IgM-MGUS and patients with stable or progressive asymptomatic Waldenström macroglobulinemia

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Tina Bagratuni, Ourania Theologi, Christos Vlachos, Ioannis Kollias, Kylee Maclachlan, Foteini Aktypi, Nefeli Mavrianou-Koutsoukou, Christine Liacos, Konstantina Taouxi, Alexandra Papadimou, Katerina Chrisostomidou, Maria Sakkou, Irene Solia, Foteini Theodorakakou, Gianmarco Favrin, Maria Gavriatopoulou, Evangelos Terpos, Marzia Varettoni, Zachary R. Hunter, Steven Treon, Francesco Maura, Meletios A. Dimopoulos, Efstathios Kastritis
Journal: Blood
Blood (2025) 146 (25): 3086–3097.
https://doi.org/10.1182/blood.2025030177
Published: 2025
Includes: Supplemental data
Journal Articles

An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden

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Erin W. Meermeier, Kirsten Pfeffer, Caleb K. Stein, Meaghen E. Sharik, Megan T. Du, Yuliza Tafoya Alvarado, Chang-Xin Shi, Yuan Xiao Zhu, P. Leif Bergsagel, Marta Chesi
Journal: Blood
Blood (2025) 146 (25): 3072–3085.
https://doi.org/10.1182/blood.2025029215
Published: 2025
Includes: Supplemental data
Journal Articles

Chronic NK cell activation results in a dysfunctional, tissue resident–like state mediated by KLF2 deficiency

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Jacob A. Myers, Rih-Sheng Huang, Shee Kwan Phung, Jeremy M. Chacón, Laura Bendzick, Anna Weis, Mihir Shetty, Taylor A. DePauw, Melissa J. Khaw, Juan E. Abrahante, Stephen D. O’Flanagan, K. Maude Ashby, John R. Lozada, Stephen C. Jameson, Justin H. Hwang, Frank Cichocki, Martin Felices, Jeffrey S. Miller
Journal: Blood
Blood (2025) 146 (25): 3059–3071.
https://doi.org/10.1182/blood.2024027763
Published: 2025
Includes: Supplemental data
Journal Articles

Rbm38 deficiency impairs erythroid heme biosynthesis and induces porphyria via reduced ferrochelatase expression

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Xinshu Xie, Ailing Zou, Lei Zhang, Xuezhen Ma, Yaohui He, Hanqi Liu, Yating Lu, Yexin Yang, Jie Ouyang, Kang Liu, Pengcheng Zhong, Ji Li, Shuqian Xu, Lifang Zhou, Bing Han, Miao Chen, Kaosheng Lv, Dingxiao Zhang, Lu Liu, Yang Mei
Journal: Blood
Blood (2025) 146 (25): 3106–3123.
https://doi.org/10.1182/blood.2025028783
Published: 2025
Includes: Supplemental data
Journal Articles

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias

Open Access
Travis J. Fleming, Mateusz Antoszewski, Sander Lambo, Michael C. Gundry, Riccardo Piussi, Lara Wahlster, Sanjana Shah, Fiona E. Reed, Kevin D. Dong, Joao A. Paulo, Steven P. Gygi, Claudia Mimoso, Seth R. Goldman, Karen Adelman, Jennifer A. Perry, Yana Pikman, Kimberly Stegmaier, Maria N. Barrachina, Kellie R. Machlus, Volker Hovestadt, Andrea Arruda, Mark D. Minden, Richard A. Voit, Vijay G. Sankaran
Journal: Blood
Blood (2025) 146 (25): 3019–3035.
https://doi.org/10.1182/blood.2025028954
Published: 2025
Includes: Supplemental data
Images
Consolidated Standards of Reporting Trials diagram.

Consolidated Standards of Reporting Trials diagram.

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in Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial > Blood
Published: 2025
Figure 1. Consolidated Standards of Reporting Trials diagram. More about this image found in Consolidated Standards of Reporting Trials diagram.
Images
Survival according to PM PET. PFS (A,C) and OS (B,D) according to PM PET response in the overall population (A-B) and in daratumumab-treated patients (C-D).

Survival according to PM PET. PFS (A,C) and OS (B,D) according to PM PET r...

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in Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial > Blood
Published: 2025
Figure 2. Survival according to PM PET. PFS (A,C) and OS (B,D) according to PM PET response in the overall population (A-B) and in daratumumab-treated patients (C-D). More about this image found in Survival according to PM PET. PFS (A,C) and OS (B,D) according to PM PET r...
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PFS and OS according to PM PET response. (A) PFS. (B) OS.

PFS and OS according to PM PET response. (A) PFS. (B) OS.

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in Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial > Blood
Published: 2025
Figure 3. PFS and OS according to PM PET response. (A) PFS. (B) OS. More about this image found in PFS and OS according to PM PET response. (A) PFS. (B) OS.
Images
Survival according to PM PET and MFC. PFS according to PM PET and MFC in the overall population (A) and in daratumumab-treated patients (B): double PET- and MFC-negative patients vs other patients.

Survival according to PM PET and MFC. PFS according to PM PET and MFC in t...

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in Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial > Blood
Published: 2025
Figure 4. Survival according to PM PET and MFC. PFS according to PM PET and MFC in the overall population (A) and in daratumumab-treated patients (B): double PET- and MFC-negative patients vs other patients. More about this image found in Survival according to PM PET and MFC. PFS according to PM PET and MFC in t...
Images
CEBPA is a target of MECOM. (A) Schematic depiction of the AID tag, followed by V5-T2A-eGFP introduced 3′ of MECOM in MUTZ3 cells. (B) Western blot analysis of a MUTZ3 AID-TIR1 clone for MECOM (upper) and β-actin (lower). Cells were treated with 500 μM auxin for indicated time spans. (C) Flow cytometric analysis of CD34 (Pe-Cy7) and CD15 (APC) staining in a MUTZ3 AID-TIR1 clone treated with auxin (100 μM, refreshed every 24 hours) after 7 days of treatment. (D) Flow cytometric analysis of a single MUTZ3 AID-TIR1 clone treated with auxin (100 μM, refreshed every 24 hours) for 7 days. Frequencies reported as percentages of single cells, based on the gates shown in panel C. (E) Stacked density histogram of eGFP expression in MUTZ3-AID T2A eGFP cells treated with auxin, with counts normalized per group. Gates and legend are shared with panels C-D. (F) Volcano plot of DEseq2 analysis on T>C-converted reads (nascent RNA; auxin vs no auxin), in 3 MUTZ3 AID OsTIR1 clones from panel B. Genes are labeled if the adjusted P value is <.01 and they are specifically upregulated in MUTZ3-MECOM-AID cells treated with auxin, but not in auxin-treated wild-type cells. (G) Volcano plot of DEseq2 analysis on MUTZ3 treated with 2 shRNAs targeting MECOM vs a scrambled control after 24 hours of puromycin selection (started 48 hours posttransduction; n = 3 for each shRNA, 2 shRNAs directed against MECOM vs 1 shRNA_control). These 2 shRNAs downregulate MECOM (as shown in plot). Genes from panel F are labeled in this plot if the adjusted P value is <.05. (H) Volcano plot of DEseq2 analysis on MUTZ3 expressing doxycycline-inducible Cas9, treated with 3 guides inactivating a GATA2 enhancer in control of MECOM (doxycycline vs no doxycycline). Previous work11 has shown these 3 guides downregulate MECOM (as shown in the plot). Genes from panel F are labeled in this plot if the adjusted P value is <.05. (I) Heat map of z scores of RNA-seq regularized log–transformed counts of MUTZ3 cells treated with control shRNA or MECOM shRNA. Only genes previously known to be upregulated by CEBPA are shown,28 grouped according to the first time point at which they are upregulated after MECOM knock-down. z scores were calculated from regularized log–transformed counts by subtracting the mean of the control samples. This heat map shows 1 of the 2 shRNAs. The other shRNA is depicted in supplemental Figure 4. APC, allophycocyanin; eGFP, enhanced green fluorescent protein; Pe-Cy7, phycoerythrin-cyanine 7; UNTX, untreated.

CEBPA is a target of MECOM. (A) Schematic depiction of the AID tag, follo...

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in MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia > Blood
Published: 2025
Figure 1. CEBPA is a target of MECOM. (A) Schematic depiction of the AID tag, followed by V5-T2A-eGFP introduced 3′ of MECOM in MUTZ3 cells. (B) Western blot analysis of a MUTZ3 AID-TIR1 clone for MECOM (upper) and β-actin (lower). Cells were treated with 500 μM auxin for indicated time spans.... More about this image found in CEBPA is a target of MECOM. (A) Schematic depiction of the AID tag, follo...
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Figure 2.

Untitled image

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in MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia > Blood
Published: 2025
Figure 2. More about this image found in Untitled image
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MECOM regulates CEBPA through its +42-kb enhancer. Volcano plot of differential chromatin accessibility (ATAC-seq) of untreated (n = 3) vs treated with auxin for 4 hours (A) and 24 hours (B) (n = 2 for both; 500 μM) calculated with DiffBind. All labels containing “CEBPA” at FDR <0.05 are labeled in bold. (C) ATAC-seq and chromatin immunoprecipitation sequencing (ChIP-seq) for indicated factors in unmodified cells (MECOM tracks from inv(3) patient and MUTZ3 bulk) and in a MUTZ3 MECOM-V5-AID OsTIR1 clone (ATAC, CTBP2, and H3K27ac), untreated and treated with auxin for indicated time points (500 μM). Genomic coordinates are hg19, and tracks are reads per kilobase per million normalized. (D) Volcano plot ATAC-seq footprinting analysis in MUTZ3-V5-AID OsTIR1 cells treated with auxin after 24 hours (n = 2), compared to untreated control (n = 4). Each dot is a single grouped motif, and motifs are colored by their cluster. Analysis performed with TOBIAS with aggregated reads in each group. (E) Composite motifs of the indicated motif clusters from panel D. FDR, false discovery rate; Inv(3) pt, MECOM/EVI1 chromatin immunoprecipitation using patient cells with an inv(3) chromosomal defect; mb, megabases.

MECOM regulates CEBPA through its +42-kb enhancer. Volcano plot of differe...

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in MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia > Blood
Published: 2025
MECOM regulates CEBPA through its +42-kb enhancer. Volcano plot of differential chromatin accessibility (ATAC-seq) of untreated (n = 3) vs treated with auxin for 4 hours (A) and 24 hours (B) (n = 2 for both; 500 μM) calculated with DiffBind. All labels containing “CEBPA” at FDR <0.05 are labeled... More about this image found in MECOM regulates CEBPA through its +42-kb enhancer. Volcano plot of differe...
Images
CEBPA repression by MECOM/CTBP complex is an essential event in 3q26-rearranged AML. (A) Flow cytometric analysis of MUTZ3 cells transduced with a lentiviral dox-inducible CEBPA construct. Cells were treated with dox (1 μg/mL) for 7 days and stained with CD15-APC and CD34-PeCy7 (day 7 shown). Flow cytometric analysis from panel A, shown at days 2 to 7. Frequencies reported as percentages of single cells, based on the gates shown in panel B (days indicated). (B) ChIP-sequencing of MECOM and CTBP2 in MUTZ3 cells. CTBP2 tracks are in MUTZ3 cells, MUTZ3+ 4× PLASS and MUTZ3+ 4× PLDLS. Data are reads per kilobase per million normalized; hg19. 4× PLASS serves as a negative control and does not outcompete CTBP2 binding to MECOM. (C) Volcano plot of DEseq analysis of 4 dox-treated pCW-4× PLDLS MUTZ3 clones vs untreated (72 hours; design: ∼ clone + condition). The horizontal line indicates a significance level of adjusted P value &lt;.05. Arrows indicate genes outside axis limits. The top 40 consistently changed genes between panels A,C are labeled (total overlapping: downregulated, 22; and upregulated, 70). (D) Bar plot of DESeq2-normalized counts for CEBPA (experiment as shown in panel A). (E) Normalized MECOM expression (RNA-seq) across a cohort of patients with AML. Samples were grouped according to a set of known molecular subtypes (CEBPA bZIP, 3q26/MECOM, inv(16), and t(8;21)) and MECOM expression. MECOM+ patients without 3q26/MECOM rearrangement were further subsetted based on the presence or absence 11q23/KMT2A rearrangement. All other subtypes are contained in the “other” category. No statistical test is shown in this plot because MECOM levels were used to define groups. (F) Normalized CEBPA expression in AML subtypes. In addition, a case with a complete CEBPA deletion and cases with CpG island methylator phenotype (characterized by a heavily methylated CEBPA promoter) were excluded from the analysis due to their complete lack of expression of CEBPA. Adjusted P values from DESeq2 are reported for indicated comparisons, and group sizes are indicated above each box plot. A dashed line indicates the median of the control group. dox, doxycycline; mb, megabases; no tx, no treatment.

CEBPA repression by MECOM/CTBP complex is an essential event in 3q26-rearr...

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in MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia > Blood
Published: 2025
Figure 3. CEBPA repression by MECOM/CTBP complex is an essential event in 3q26-rearranged AML. (A) Flow cytometric analysis of MUTZ3 cells transduced with a lentiviral dox-inducible CEBPA construct. Cells were treated with dox (1 μg/mL) for 7 days and stained with CD15-APC and CD34-PeCy7 (da... More about this image found in CEBPA repression by MECOM/CTBP complex is an essential event in 3q26-rearr...
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Incidence of LEF1 alterations in T-ALL across the pediatric FRALLE-2000 and adult GRAALL 2003-2005 trials. (A) The incidence of LEF1 gene alterations among patients with T-ALL at diagnosis across the FRALLE-2000 and GRAALL 2003-2005 studies (left). The type of genetic alterations and their frequencies (right). (B) Lollipop plots indicating the observed LEF1 mutations and their consequences in the FRALLE-2000 and GRAALL 2003-2005 trials. (C) Copy number variant assessment in array comparative genomic hybridization showing focal exon 2-3 LEF1 deletion (left) and large LEF1 deletion (right). (D) Bars map the observed chromosomal deletions involving the LEF1 gene in the FRALLE-2000 and GRAALL 2003-2005 trials and reveal a minimal deleted region.

Incidence of LEF1 alterations in T-ALL across the pediatric FRALLE-2000 a...

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in LEF1 intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL > Blood
Published: 2025
Figure 1. Incidence of LEF1 alterations in T-ALL across the pediatric FRALLE-2000 and adult GRAALL 2003-2005 trials. (A) The incidence of LEF1 gene alterations among patients with T-ALL at diagnosis across the FRALLE-2000 and GRAALL 2003-2005 studies (left). The type of genetic alterations a... More about this image found in Incidence of LEF1 alterations in T-ALL across the pediatric FRALLE-2000 a...
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Clinical impact of LEF1 alterations in the pediatric FRALLE-2000 and adult GRAALL 2003-2005 trials. OS (A) and cumulative incidence of relapse (B) in the FRALLE-2000 and GRAALL 2003-2005 trials. Red curves represent the patients with LEF1-altered T-ALL, and blue curves represent the WT patients. ALT, altered.

Clinical impact of LEF1 alterations in the pediatric FRALLE-2000 and adul...

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in LEF1 intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL > Blood
Published: 2025
Figure 2. Clinical impact of LEF1 alterations in the pediatric FRALLE-2000 and adult GRAALL 2003-2005 trials. OS (A) and cumulative incidence of relapse (B) in the FRALLE-2000 and GRAALL 2003-2005 trials. Red curves represent the patients with LEF1 -altered T-ALL, and blue curves represent th... More about this image found in Clinical impact of LEF1 alterations in the pediatric FRALLE-2000 and adul...
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The oncogenetic landscape of LEF1-altered T-ALL. (A) Oncoplot illustrating the genetic anomalies found in LEF1-WT and LEF1-altered T-ALL cases from the FRALLE-2000 and GRAALL 2003-2005 studies. Each column represents an individual case, annotated with defining genetic and oncogenomic alterations. Genes are grouped by their functional categories. The right panel shows the overall frequency of alterations per gene in LEF1-WT and LEF1-altered patients. (B) Representation of the alteration frequencies for the genes significantly differentially altered in LEF1-WT vs mutated, Del2/3, or deleted patients across FRALLE-2000 and GRAALL 2003-2005 trials. Statistical differences were assessed using the Fisher test. ∗∗P &lt; .01; ∗∗∗P &lt; .001. (C) Distribution of gene alterations by functional pathways in LEF1-WT vs mutated, Del2/3, or deleted patients in the FRALLE-2000 and GRAALL 2003-2005 trials. ALT, altered.

The oncogenetic landscape of LEF1 -altered T-ALL. (A) Oncoplot illustrati...

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in LEF1 intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL > Blood
Published: 2025
Figure 3. The oncogenetic landscape of LEF1 -altered T-ALL. (A) Oncoplot illustrating the genetic anomalies found in LEF1 -WT and LEF1 -altered T-ALL cases from the FRALLE-2000 and GRAALL 2003-2005 studies. Each column represents an individual case, annotated with defining genetic and oncogen... More about this image found in The oncogenetic landscape of LEF1 -altered T-ALL. (A) Oncoplot illustrati...