Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency
While therapies targeting CD19 by antibodies, chimeric antigen receptor T cells (CAR-T), and T cell engagers have improved the response rates in B cell malignancies, the emergence of resistant cell populations with low CD19 expression can lead to relapsed disease. We developed an in vitro model of adaptive resistance facilitated by chronic exposure of leukemia cells to a CD19 immunotoxin. Single-cell RNA-Seq (scRNA-Seq) showed an increase in transcriptionally distinct CD19lo populations among resistant cells. Mass cytometry demonstrated that CD22 was also decreased in these CD19lo-resistant cells. An assay for transposase-...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Sarah Aminov, Orsi Giricz, David T. Melnekoff, R. Alejandro Sica, Veronika Polishchuk, Cristian Papazoglu, Bonnie Yates, Hao-Wei Wang, Srabani Sahu, Yanhua Wang, Shanisha Gordon-Mitchell, Violetta V. Leshchenko, Carolina Schinke, Kith Pradhan, Srinivas Al Source Type: research
Oncotherapy resistance explained by Darwinian and Lamarckian models
Cell and antibody therapies directed against surface molecules on B cells, e.g., CD19-targeting chimeric antigen receptor T cells (CD19 CAR-T), are now standard for patients with chemorefractory B cell acute lymphoblastic leukemias and other B cell malignancies. However, early relapse rates remain high. In this issue of the JCI, Aminov, Giricz, and colleagues revealed that leukemia cells resisting CD19-targeted therapy had reduced CD19 but also low CD22 expression and were sensitive to Bruton’s tyrosine kinase and/or MEK inhibition. Overall, their observations support the evolution of resistance following a Lamarckian mo...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Yogen Saunthararajah Source Type: research
Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor–ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, ev...
Source: Journal of Clinical Investigation - April 15, 2024 Category: Biomedical Science Authors: Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W. Zimmerman, Thomas Eder, Diaaeldin I. Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Dani Source Type: research
Malformation of the endoplasmic reticulum system evolving into giant inclusions and Auer bodies in acute promyelocytic leukemia: an ultrastructural study of 6 cases
This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system. This paper reveals that in the promyeloblasts of APL, ER is the source of and transforms progressively into giant inclusions and Auer bodies.PMID:38619116 | DOI:10.1080/01...
Source: Ultrastructural Pathology - April 15, 2024 Category: Pathology Authors: Yong-Xin Ru Shu-Xu Dong Jing Liu Jin-Hua Liu Yuan Zhou Brian Eyden Source Type: research
< em > SH2B3 < /em > alterations in a novel genetic condition, juvenile myelomonocytic leukemia, and myeloproliferative neoplasia
Haematologica. 2024 Apr 11. doi: 10.3324/haematol.2023.284747. Online ahead of print.ABSTRACTNot available.PMID:38618667 | DOI:10.3324/haematol.2023.284747 (Source: Haematologica)
Source: Haematologica - April 15, 2024 Category: Hematology Authors: Charlotte M Niemeyer Miriam Erlacher Source Type: research
Molecular responses in decitabine- and decitabine/venetoclax-treated patients with acute myeloid leukemia and myelodysplastic syndromes
Haematologica. 2024 Apr 11. doi: 10.3324/haematol.2022.281396. Online ahead of print.ABSTRACTNot available.PMID:38618679 | DOI:10.3324/haematol.2022.281396 (Source: Haematologica)
Source: Haematologica - April 15, 2024 Category: Hematology Authors: Agata Gruszczynska Abhishek Maiti Christopher A Miller Sai Mukund Ramakrishnan Daniel C Link Geoffrey L Uy Allegra A Petti Kala Hayes Courtney D DiNardo Farhad Ravandi Timothy J Ley David H Spencer Feng Gao Marina Y Konopleva John S Welch Source Type: research
Bi-clonal Chronic Lymphocytic Leukemia
(Source: Indian Journal of Hematology and Blood Transfusion)
Source: Indian Journal of Hematology and Blood Transfusion - April 15, 2024 Category: Hematology Source Type: research
Correction to: Histone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors
Leukemia, Published online: 15 April 2024; doi:10.1038/s41375-024-02185-yCorrection to: Histone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors (Source: Leukemia)
Source: Leukemia - April 15, 2024 Category: Hematology Authors: Jooeun Bae Teru Hideshima Yu-Tzu Tai Yan Song Paul Richardson Noopur Raje Nikhil C. Munshi Kenneth C. Anderson Source Type: research
Viruses, Vol. 16, Pages 614: Evaluation of a Revised Point-of-Care Test for the Detection of Feline Leukaemia p27 Antigen and Anti-p15E Antibodies in Cats
This study aimed to assess this PoC test&rsquo;s performance concerning FeLV p27 antigen and FeLV anti-p15E antibody detection. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were assessed after ten minutes (recommended) and 20 min (prolonged) incubation times. The test results were evaluated as either positive or negative. Serum samples from 934 cats were included, originating from Italy (n = 269), Portugal (n = 240), Germany (n = 318), and France (n = 107). FeLV p27 antigen and anti-p15E antibodies were measured by reference standard ELISAs and compared to the PoC test results. The P...
Source: Viruses - April 15, 2024 Category: Virology Authors: Juliana Giselbrecht St éphanie Jähne Mich èle Bergmann Marina L. Meli Svenja Teichmann-Knorrn Yury Zablotski Maria-Grazia Pennisi Nicolas Layachi Rodrigo Serra Stefano Bo Regina Hofmann-Lehmann Katrin Hartmann Tags: Article Source Type: research
Adult survivors ’ perception of their childhood and the influences of being treated for acute lymphoblastic leukaemia with allogenic hematopoietic stem cell transplantation as a child: a phenomenographic study
Adults who had acute lymphoblastic leukaemia (ALL) as children and were treated with allogeneic hematopoietic stem cell transplantation (aHSCT) may have been affected in their lives due to several long-term complications. From a clinical point of view, it is of interest to study how survivors describe their perceptions of their childhood today. The aim was therefore to describe how adults perceived their childhood and the influences of being treated for ALL with aHSCT as a child. (Source: European Journal of Oncology Nursing)
Source: European Journal of Oncology Nursing - April 15, 2024 Category: Cancer & Oncology Authors: Susann Arvidsson, Elisabeth Brobeck, Jens Nygren, Marianne Jarfelt, Katarina Aili, Maria Olsson Source Type: research
T cell-mediated tumor killing sensitivity gene signature-based prognostic score for acute myeloid leukemia
ConclusionA T-cell mediated killing sensitivity gene-based prognostic score TTKPI showed good accuracy in predicting survival in AML. TTKPI corresponded to functional and immunological features of the tumor microenvironment including checkpoint expression patterns and should be investigated for precision medicine approaches. (Source: Hormones and Cancer)
Source: Hormones and Cancer - April 15, 2024 Category: Cancer & Oncology Source Type: research
Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia
ConclusionOverall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies. (Source: Journal of Huazhong University of Science and Technology -- Medical Sciences --)
Source: Journal of Huazhong University of Science and Technology -- Medical Sciences -- - April 15, 2024 Category: Research Source Type: research
Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia
CONCLUSION: Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.PMID:38615511 | DOI:10.1016/j.imbio.2024.152804 (Source: Immunobiology)
Source: Immunobiology - April 14, 2024 Category: Allergy & Immunology Authors: Shiyi Pan Qinghua Cai Yiqiong Wei Haifeng Tang Yuping Zhang Wei Zhou Tingfen Deng Wenjian Mo Shunqing Wang Caixia Wang Cunte Chen Source Type: research
GSE239468 Condensate-promoting ENL mutation induces tumorigenesis via chromatin remodeling [ChIP-seq and CUT & Tag]
Contributors : Liling Wan ; Yiman Liu ; Qinglan LiSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusGain-of-function mutations in the chromatin ‘reader’ ENL, identified in AML and Wilms tumor, have been shown to induce aberrant formation of transcriptional condensates in cellular systems. However, the precise role of these mutations and their condensate forming property in tumorigenesis remains unclear. By creating a conditional knock-i n mouse model for the most prevalent ENL mutation, we establish ENL mutant as a bona fide oncogenic driver of acute myeloid leukemi...
Source: GEO: Gene Expression Omnibus - April 14, 2024 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
GSE239469 Condensate-promoting ENL mutation induces tumorigenesis via chromatin remodeling [RNA-seq]
Contributors : Liling Wan ; Yiman Liu ; Qinglan LiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGain-of-function mutations in the chromatin ‘reader’ ENL, identified in AML and Wilms tumor, have been shown to induce aberrant formation of transcriptional condensates in cellular systems. However, the precise role of these mutations and their condensate forming property in tumorigenesis remains unclear. By creating a conditional knock-i n mouse model for the most prevalent ENL mutation, we establish ENL mutant as a bona fide oncogenic driver of acute myeloid leukemia in vivo. Het...
Source: GEO: Gene Expression Omnibus - April 14, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
