Article
Multidisciplinary Sciences
Tatiana Subkhankulova, Karen Camargo Sosa, Leonid A. Uroshlev, Masataka Nikaido, Noah Shriever, Artem S. Kasianov, Xueyan Yang, Frederico S. L. M. Rodrigues, Thomas J. Carney, Gemma Bavister, Hartmut Schwetlick, Jonathan H. P. Dawes, Andrea Rocco, Vsevolod J. Makeev, Robert N. Kelsh
Summary: Neural crest cells are highly multipotent stem cells, and it is still unclear how their fate restriction to specific fates occurs. This study shows that in zebrafish, broad multipotency is retained even after migration, suggesting that fate restriction occurs directly but dynamically.
NATURE COMMUNICATIONS
(2023)
Article
Cell & Tissue Engineering
Ann-Kathrin Fanti, Katrin Busch, Alessandro Greco, Xi Wang, Branko Cirovic, Fuwei Shang, Tamar Nizharadze, Larissa Frank, Melania Barile, Thorsten B. Feyerabend, Thomas Hoefer, Hans-Reimer Rodewald
Summary: In response to infections and stress, hematopoiesis rapidly enhances blood and immune cell production. The specific stage responsible for this regeneration was unclear, but experiments on mice showed that hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) played different roles. HSCs responded to sepsis by increasing proliferation and cell death, while MPPs were identified as a major source for accelerated myeloid cell production. This suggests that progenitors, rather than stem cells, regulate blood and immune cell homeostasis to ensure a rapid response and maintain the integrity of the HSC population.
Article
Cell Biology
Tessa Dignum, Barbara Varnum-Finney, Sanjay R. Srivatsan, Stacey Dozono, Olivia Waltner, Adam M. Heck, Takashi Ishida, Cynthia Nourigat-McKay, Dana L. Jackson, Shahin Rafii, Cole Trapnell, Irwin D. Bernstein, Brandon Hadland
Summary: This study demonstrates that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSCs. HSC-competent HE are characterized by expression of CXCR4 surfacemarker and higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal.
Article
Cell Biology
Mariangela Scalise, Fabiola Marino, Luca Salerno, Nunzia Amato, Claudia Quercia, Chiara Siracusa, Andrea Filardo, Antonio Chiefalo, Loredana Pagano, Giuseppe Misdea, Nadia Salerno, Antonella De Angelis, Konrad Urbanek, Giuseppe Viglietto, Daniele Torella, Eleonora Cianflone
Summary: Three-dimensional cell culture systems, particularly stem-cell-derived spheroids, show great potential for studying tissue biology and disease. This study compared three different scaffold-free systems for cardiac stem cell/progenitor-derived spheroid formation and cardiomyocyte commitment, and found that a 3D culture environment is essential for robust cardiomyocyte differentiation.
Article
Oncology
Naval Daver, Alexander E. Perl, Joseph Maly, Mark Levis, Ellen Ritchie, Mark Litzow, James McCloskey, Catherine C. Smith, Gary Schiller, Terrence Bradley, Ramon Tiu, Kiran Naqvi, Monique Dail, Deanna Brackman, Satya Siddani, Jing Wang, Brenda Chyla, Paul Lee, Jessica K. Altman
Summary: Combining gilteritinib with venetoclax has shown promising results in treating relapsed/refractory FLT3-mutated AML, with high rates of response and molecular remission regardless of prior FLT3 inhibitor therapy.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, General & Internal
Ismael F. Alarbeed, Abdulsamad Wafa, Faten Moassass, Bassel Al-Halabi, Walid Al-Achkar, Thomas Liehr, Imad Aboukhamis
Summary: This study reports a case of a 54-year-old Arab male with AML who had two new mutations in FLT3-ITDs and an NPM1 mutation. The patient underwent cytogenetic and molecular genetic testing. While the first round of chemotherapy was successful, the patient unfortunately relapsed and died one month after initial diagnosis.
JOURNAL OF MEDICAL CASE REPORTS
(2021)
Article
Oncology
Pierre-Yves Dumas, Arnaud Villacreces, Amelie V. Guitart, Ali El-habhab, Layal Massara, Olivier Mansier, Audrey Bidet, Delphine Martineau, Solene Fernandez, Thibaut Leguay, Arnaud Pigneux, Isabelle Vigon, Jean-Max Pasquet, Vanessa Desplat
Summary: The study revealed that gilteritinib exhibited a stronger proapoptotic effect on FLT3-ITD AML cells in a simulated bone marrow microenvironment compared to quizartinib, and was more effective at targeting leukemia cells. Additionally, gilteritinib showed a toxicity profile on normal murine hematopoiesis similar to quizartinib.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Corinna Spohr, Teresa Poggio, Geoffroy Andrieux, Katharina Schoenberger, Nina Cabezas-Wallscheid, Melanie Boerries, Sebastian Halbach, Anna L. Illert, Tilman Brummer
Summary: The presence of internal tandem duplications (ITD) in FMS-like tyrosine kinase 3 (FLT3) combined with DNMT3A mutations in acute myeloid leukemia (AML) leads to poor prognosis. Studies have shown that GAB2 is essential for the development of Flt3-ITD driven AML, with Gab2 deficient mice displaying prolonged survival and reduced pathology. Gab2 increases signaling of receptor tyrosine kinases, promoting AML aggressiveness and drug resistance, making it a promising biomarker and therapeutic target in human AML.
Review
Cell Biology
Yongfeng Chen, Zhenyou Zou, Mihnea-Alexandru Gaman, Linglong Xu, Jing Li
Summary: FLT3-ITD is the most common genetic change in acute myeloid leukemia (AML), and about 30% of all AMLs have a FLT3-ITD mutation. FLT3 inhibitors have shown promising effects in FLT3-ITD-mutated AML, but drug resistance limits the clinical response. Evidence suggests that FLT3-ITD triggers oxidative stress signaling, which plays a pivotal role in drug resistance. Downstream pathways of FLT3-ITD, including STAT5, PI3K/AKT, and RAS/MAPK, are major oxidative stress signaling pathways.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Xiaolin Yin, Minran Zhou, Lu Zhang, Yue Fu, Man Xu, Xiaoming Wang, Zelong Cui, Zhenxing Gao, Miao Li, Yuting Dong, Huimin Feng, Sai Ma, Chunyan Chen
Summary: ASF1A was found to be aberrantly expressed in CML-BC patients and enhanced the transformation to CML-BC by mediating cell differentiation arrest. This study also revealed that ASF1A functions as a coactivator of the Notch transcriptional complex, enhancing Notch signaling activation to mediate differentiation arrest in CML cells. These findings suggest that targeting ASF1A might represent a promising therapeutic approach and ASF1A could serve as a biomarker for disease progression in CML patients.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Hanlin Wang, Guanghao Luo, Xiaobei Hu, Gaoya Xu, Tao Wang, Minmin Liu, Xiaohui Qiu, Jianan Li, Jingfeng Fu, Bo Feng, Yutong Tu, Weijuan Kan, Chang Wang, Ran Xu, Yubo Zhou, Jianmin Yang, Jia Li
Summary: By analyzing data from primary AML patient samples, C/EBP alpha activation is identified as a major mechanism of resistance to FLT3 inhibitors (FLT3i). Inactivation of C/EBP alpha enhances the efficacy of FLT3i, and the antihypertensive medication guanfacine mimics the inactivation of C/EBP alpha, showing a synergistic effect with FLT3i. These findings highlight the targetability of C/EBP alpha activation as a mechanism of resistance and support clinical studies to test the combination of guanfacine with FLT3i.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Maria-Riera Pique-Borras, Zivojin Jevtic, Frederik Otzen Bagger, Jonathan Seguin, Rathick Sivalingam, Matheus Filgueira Bezerra, Amber Louwagie, Sabine Juge, Ioannis Nellas, Robert Ivanek, Alexandar Tzankov, Ute M. Moll, Oriano Cantillo, Ramona Schulz-Heddergott, Alexandre Fagnan, Thomas Mercher, Juerg Schwaller
Summary: The NFIA-ETO2 fusion is a chromosomal translocation found exclusively in pediatric patients with pure erythroid leukemia (PEL). The fusion protein impairs erythroid differentiation and promotes proliferation in murine erythroblasts and fetal liver-derived erythroblasts. However, it does not induce disease upon transplantation into mice. In the presence of TP53(R248Q) mutation, NFIA-ETO2 acquires clonogenic activity and induces a transplantable PEL-like disease. Molecular studies reveal that NFIA-ETO2 represses erythroid differentiation by targeting genes with NFI binding sites and ETO2 modifications, while TP53(R248Q) enhances self-renewal and survival potential.
Article
Biochemistry & Molecular Biology
Victoria Michaels, Smahane Chalabi, Agnes Legrand, Julie Renard, Emmanuel Tejerina, Marina Daouya, Sylvie Fabrega, Jerome Megret, Robert Olaso, Anne Boland, Jean-Francois Deleuze, Christophe Battail, Diana Tronik-Le Roux, Sophie Ezine
Summary: T cells have the potential to maintain immunological memory and self-tolerance. Delayed T cell reconstitution is a common issue in hematopoietic stem cell transplantation. To overcome this difficulty, a new approach using DNA barcoding strategy was developed to identify populations with efficient lymphoid reconstitution properties. Results highlight the role of LMPP progenitors for lymphoid generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Zhimin Gu, Yuxuan Liu, Yuannyu Zhang, Hui Cao, Junhua Lyu, Xun Wang, Annika Wylie, Simon J. Newkirk, Amanda E. Jones, Michael Lee, Giovanni A. Botten, Mi Deng, Kathryn E. Dickerson, Cheng Cheng Zhang, Wenfeng An, John M. Abrams, Jian Xu
Summary: MPHOSPH8 loss inhibits the development of acute myeloid leukemia by reactivating LINE-1 retrotransposons, which induces DNA damage response and cell cycle exit in AML cells. The study also shows that AML oncogenic mutations promote L1 suppression, and enhanced L1 silencing is associated with poor prognosis in human AML.
Article
Cell Biology
Ho Sun Jung, Gene Uenishi, Mi Ae Park, Peng Liu, Kran Suknuntha, Matthew Raymond, Yoon Jung Choi, James A. Thomson, Irene M. Ong, Igor I. Slukvin
Summary: The research findings suggest that SOX17 is a key regulator in linking arterial and HOXA programs in hemogenic endothelium (HE) in humans, playing a crucial role in the specification of HE with robust lympho-myeloid potential. This understanding may contribute to better programming of hematopoietic stem cell fate from human pluripotent stem cells.
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Review
Hematology
Jennifer Mary O'Sullivan, Adam J. Mead, Bethan Psaila
Summary: Myeloproliferative neoplasms (MPN) are a group of hematopoietic malignancies driven by aberrant JAK/STAT signaling. Cellular heterogeneity at the single-cell level provides new insights into MPN biology, which can help predict clinical course and improve treatment strategies for these cancers, leading to better outcomes for patients.
Meeting Abstract
Hematology
Rong Li, Michela Colombo, Guanlin Wang, Sally-Ann Clark, Antonio Rodriguez-Romera, Yiran Meng, Abdullah Khan, Wei Xiong Wen, Nikolaos Sousos, Lauren Murphy, Christina Simoglou Karali, Korsuk Sirinukunwattana, Jennifer O'Sullivan, Ruggiero Norfo, Qian Cheng, Charlotte Brierley, Joana Carrelha, Zemin Ren, Gabriel A. Rabinovich, Vijay A. Rathinam, Supat Thongjuea, Daniel Royston, Adam J. Mead, Bethan Psaila
Article
Hematology
Christian Pecquet, Nicolas Papadopoulos, Thomas Balligand, Ilyas Chachoua, Amandine Tisserand, Audrey Nedelec, Didier Vertommen, Anita Roy, Caroline Marty, Harini Nivarthi, Mira El-Khoury, Eva Hug, Andrea Majoros, Erica Xu, Oleh Zagrijtschuk, Tudor E. Fertig, Daciana S. Marta, Heinz Gisslinger, Bettina Gisslinger, Martin Schalling, Ilaria Casetti, Elisa Rumi, Daniela Pietra, Chiara Cavalloni, Luca Arcaini, Mario Cazzola, Norio Komatsu, Yoshihiko Kihara, Yoshitaka Sunami, Yoko Edahiro, Marito Araki, Roman Lesyk, Veronika Buxhofer-Ausch, Sonja Heibl, Florence Pasquier, Violaine Havelange, Isabell Plo, William Vainchenker, Robert Kralovics, Stefan N. Constantinescu
Summary: Mutant CALR proteins bind to and activate the TpoR in cells, driving the development of myeloproliferative neoplasms. These mutant CALR proteins can be found in patient plasma complexed with sTFR1, which increases their stability. They can specifically interact with TpoR on target cells and promote thrombopoietin-independent colony formation.
Correction
Oncology
Hosuk Ryou, Korsuk Sirinukunwattana, Alan Aberdeen, Gillian Grindstaff, Bernadette J. Stolz, Helen Byrne, Heather A. Harrington, Nikolaos Sousos, Anna L. Godfrey, Claire N. Harrison, Bethan Psaila, Adam J. Mead, Gabrielle Rees, Gareth D. H. Turner, Jens Rittscher, Daniel Royston
Article
Biochemistry & Molecular Biology
Wei Xiong Wen, Adam J. Mead, Supat Thongjuea
Summary: A comprehensive R package called MARVEL was developed for single-cell splicing analysis. Extensive benchmarking and analysis of publicly available datasets demonstrated the importance and utility of MARVEL in single-cell research, enabling systematic analysis of splicing and gene expression to reveal biological insights.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
John Mascarenhas, Marina Kremyanskaya, Andrea Patriarca, Francesca Palandri, Timothy Devos, Francesco Passamonti, Raajit K. Rampal, Adam J. Mead, Gabriella Hobbs, Joseph M. Scandura, Moshe Talpaz, Nikki Granacher, Tim C. P. Somervaille, Ronald Hoffman, Marielle J. Wondergem, Mohamed E. Salama, Gozde Colak, Jike Cui, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Natalia Curto-Garcia, Claire Harrison, Vikas Gupta
Summary: In patients with myelofibrosis who are naive to JAKi treatment, the rational combination of the BET inhibitor pelabresib and ruxolitinib showed good tolerability and durable improvements in spleen and symptom burden.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Yiran Meng, Joana Carrelha, Roy Drissen, Xiying Ren, Bowen Zhang, Adriana Gambardella, Simona Valletta, Supat Thongjuea, Sten Eirik Jacobsen, Claus Nerlov
Summary: The lymphoid fate in haematopoietic stem cells is determined through epigenetic programming rather than transcriptional control, which also influences the differentiation pathways of platelets with distinct kinetics.
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Nicolas Papadopoulos, Audrey Nedelec, Allison Derenne, Teodor Asvadur Sulea, Christian Pecquet, Ilyas Chachoua, Gaelle Vertenoeil, Thomas Tilmant, Andrei-Jose Petrescu, Gabriel Mazzucchelli, Bogdan I. Iorga, Didier Vertommen, Stefan N. Constantinescu
Summary: In myeloproliferative neoplasms, frameshift mutants of calreticulin turn into rogue cytokines by inducing constitutive activation of the Thrombopoietin Receptor (TpoR). Here, the authors define how mutant calreticulin acquires specificity for TpoR binding and triggers its constitutive activation.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Sylvie D. Freeman, Abin Thomas, Ian Thomas, Robert K. Hills, Paresh Vyas, Amanda Gilkes, Marlen Metzner, Niels Asger Jakobsen, Alison Kennedy, Rachel Moore, Nuria Marquez Almuina, Sarah Burns, Sophie King, Georgia Andrew, Kathleen M. E. Gallagher, Rob S. Sellar, Paul Cahalin, Duruta Weber, Mike Dennis, Priyanka Mehta, Steven Knapper, Nigel H. Russell
Summary: Addition of gemtuzumab ozogamicin to induction chemotherapy improves outcomes in older AML patients, especially those with MRD<0.1% and IDH mutations. The survival advantage from this treatment is dependent on allogeneic transplantation.
Article
Hematology
Sahoko Matsuoka, Raffaella Facchini, Tiago C. Luis, Joana Carrelha, Petter S. Woll, Takuo Mizukami, Bishan Wu, Hanane Boukarabila, Mario Buono, Ruggiero Norfo, Fumio Arai, Toshio Suda, Adam J. Mead, Claus Nerlov, Sten Eirik W. Jacobsen
Summary: This study investigates the critical regulatory role of hematopoietic stem cell (HSC) vascular niches in the bone marrow, particularly the expression of KIT ligand by endothelial niche cells. The findings suggest that both soluble and membrane-bound forms of endothelial-derived KIT ligand contribute to HSC regulation, but more specific tools are needed to understand the niche-specific roles of regulatory cues in hematopoietic niche cells.
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Summary: In this study, the researchers uncover a feedback mechanism in which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Edyta E. Wojtowicz, Jayna J. Mistry, Vladimir Uzun, Charlotte Hellmich, Anita Scoones, Desmond W. Chin, Laura M. Kettyle, Francesca Grasso, Allegra M. Lord, David J. Wright, Graham J. Etherington, Petter S. Woll, Mirjam E. Belderbos, Kristian M. Bowles, Claus Nerlov, Wilfried Haerty, Leonid V. Bystrykh, Sten Eirik W. Jacobsen, Stuart A. Rushworth, Iain C. Macaulay
Summary: This study investigates the clonal dynamics of hematopoietic stem cells in the production of platelets and erythrocytes. The results show dynamic shifts of clonal behaviors over time and reveal that acute platelet depletion leads to exclusive production of platelets by multipotent hematopoietic stem cells. Additionally, the study identifies the emergence of new myeloid-biased clones supporting the production of blood cells.
Meeting Abstract
Hematology
Alba Rodriguez-Meira, Ruggiero Norfo, Wei Wen, Agathe Chedeville, Haseeb Rahman, Jennifer O'Sullivan, Guanlin Wang, Eleni Louka, Warren Kretzschmar, Aimee Paterson, Charlotte Brierley, Jean-Edouard Martin, Caroline Demeule, Matthew Bashton, Nikolaos Sousos, Angela Hamblin, Helene Guermouche, Florence Pasquier, Christophe Marzac, Francois Girodon, Mark Drummond, Claire Harrison, Isabelle Plo, Sten Eirik Jacobsen, Bethan Psaila, Supat Thongjuea, Ileana Antony-Debre, Adam Mead
EXPERIMENTAL HEMATOLOGY
(2022)