Review
Oncology
Ajay Abraham, William Matsui
Summary: Myeloid malignancies arise from normal hematopoiesis and the Hedgehog (HH) signaling pathway plays an important role in these diseases, with SMO inhibitors approved for the treatment of acute myeloid leukemia (AML). Despite the broad activity of SMO inhibitors in AML, clinical studies in other myeloid malignancies remain inconclusive and further research is needed to explore their efficacy.
Article
Biochemistry & Molecular Biology
Alhomidi Almotiri, Ashleigh S. Boyd, Neil P. Rodrigues
Summary: Zeb1 plays a critical role in regulating the absolute cell number and function of lympho-myeloid primed progenitors (LMPPs), influencing the differentiation potential of HSCs and selection of hematopoietic lineages. Competitive transplantation analysis reveals a reduction in engraftment to hematopoietic organs from Zeb1-deficient mice, indicating the important role of Zeb1 in regulating LMPP differentiation potential in the context of transplantation.
Article
Biochemistry & Molecular Biology
Chin-Kai Chuang, Su-Fen Chen, Yu-Hsiu Su, Wei-Hsin Chen, Wei-Ming Lin, I-Ching Wang, Song-Kun Shyue
Summary: Three waves of hematopoiesis occur in the mouse embryo, including primitive hematopoiesis, extra embryonic pro-definitive hematopoiesis, and embryonic definitive hematopoiesis. The SCL-L isoform is necessary for the launch of definitive hematopoiesis, while SCL-S is sufficient to sustain primitive hematopoiesis. The loss of SCL-L leads to the development of only the endothelial lineage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Olivia Arnold, Karina Barbosa, Aniruddha J. Deshpande, Nan Zhu
Summary: DOT1L plays a crucial role in normal and malignant hematopoiesis, and its aberrant activity is implicated in the development of hematopoietic malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Xia Wu, Wu Ye, Yuping Gong
Summary: METTL3 is a core methyltransferase involved in m(6)A modification and plays a vital role in normal and malignant hematopoiesis. It affects the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors in hematological neoplasms. Inhibitors of METTL3, such as STM2457, have shown potential in treating acute myeloid leukemia by blocking proliferation and promoting differentiation and apoptosis of cancer cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Muxin Gu, Sruthi Cheloor Kovilakam, William G. Dunn, Ludovica Marando, Clea Barcena, Irina Mohorianu, Alexandra Smith, Siddhartha P. Kar, Margarete A. Fabre, Moritz Gerstung, Catherine A. Cargo, Luca Malcovati, Pedro M. Quiros, George S. Vassiliou
Summary: This study analyzes data from UK Biobank participants and finds that the risk of developing different types of myeloid neoplasms can be detected years before diagnosis. The authors develop a predictive model that integrates somatic gene mutations with blood test parameters, which could guide future strategies for early detection and prevention of these diseases.
Article
Cell Biology
Oscar A. Pena, Alexandra Lubin, Jasmine Rowell, Yvette Hoade, Noreen Khokhar, Hanna Lemmik, Christopher Mahony, Phoebe Dace, Chianna Umamahesan, Elspeth M. Payne
Summary: Germline loss or mutation of one copy of the transcription factor GATA2 in humans results in clinical phenotypes affecting hematopoietic, lymphatic, and vascular systems. In this research, zebrafish with two copies of the Gata2 gene were used to investigate the effects of these genes on hematopoiesis during development, revealing unique roles at different stages and a potential redundancy between the two genes. The study also showed defects in the myeloid compartment in adult zebrafish with combined heterozygosity loss, similar to GATA2 loss in humans, adding to our understanding of GATA2 deficiency and its developmental effects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sayantani Sinha, Joana Pereira-Reis, Amaliris Guerra, Stefano Rivella, Delfim Duarte
Summary: Iron is essential for maintaining normal hematopoiesis and erythropoiesis, but excessive iron can lead to toxic effects. Recent advances involve understanding key iron regulators and the development of new drugs for hematological disorders. Future studies will need to continue exploring the role of iron in both normal and malignant hematopoiesis.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Review
Biochemistry & Molecular Biology
Agata Szade, Krzysztof Szade, Mahdi Mahdi, Alicja Jozkowicz
Summary: The hematopoietic system is regulated by HO-1, impacting hematopoietic stem cells, endothelial cells, and immune responses. HO-1 plays a crucial role in maintaining the periodicity and function of blood cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Oncology
Alejandro Ferrer, Abhishek A. Mangaonkar, Mrinal M. Patnaik
Summary: This review summarizes recent studies on patient cohorts with telomere biology disorders (TBDs), describing their myeloid transformation events and efforts to develop screening and treatment guidelines. Preliminary studies indicate that TBD patients have a higher prevalence of somatic genetic alterations, increasing their predisposition to myeloid neoplasms (MNs). The mutational landscape in TBD differs from that observed in non-TBD patients, and certain events such as hypocellular bone marrows are common. However, further research is needed to elucidate the mechanisms of MN development.
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2022)
Article
Cell Biology
Minghao Li, Yanjie Lan, Juan Gao, Shengnan Yuan, Shuaibing Hou, Tengxiao Guo, Fei Zhao, Yuxia Wang, Weiping Yuan, Xiaomin Wang
Summary: Rapamycin promotes the expansion of myeloid lineage by inducing the production of G-CSF, but intraperitoneal administration may impair myeloid cell differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Margherita Sisto, Domenico Ribatti, Sabrina Lisi
Summary: Recent advances in understanding the molecular pathways linking inflammation with organ fibrosis and autoimmune diseases have identified EMT as a common association. The chronic inflammatory microenvironment plays a crucial role in inducing pathological EMT, with TGF-beta being a key player in fibrosis induction. Further research aims to target EMT-dependent fibrosis in autoimmune diseases through a better understanding of molecular responses to inflammatory signals.
Article
Cell & Tissue Engineering
Yasuhiro Shingai, Takafumi Yokota, Daisuke Okuzaki, Takao Sudo, Tomohiko Ishibashi, Yukiko Doi, Tomoaki Ueda, Takayuki Ozawa, Ritsuko Nakai, Akira Tanimura, Michiko Ichii, Hirohiko Shibayanna, Yuzuru Kanakura, Naoki Hosen
Summary: The heterogeneity of AML cells, including varying ESAM expression levels, can be mutually interconverted and regulated by the activation of the TGF beta signaling pathway. Inhibition of TGF beta signaling not only blocks the phenotypic variation of AML cells, but also hinders their proliferation, making it a potential therapeutic target for AML.
Article
Hematology
Tim Grob, Adil S. A. Al Hinai, Mathijs A. Sanders, Francois G. Kavelaars, Melissa Rijken, Patrycja L. Gradowska, Bart J. Biemond, Dimitri A. Breems, Johan Maertens, Marinus van Marwijk Kooy, Thomas Pabst, Okke de Weerdt, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht, Gerwin A. Huls, Jan J. Cornelissen, H. Berna Beverloo, Bob Lowenberg, Mojca Jongen-Lavrencic, Peter J. M. Valk
Summary: Mutant TP53 AML and MDS-EB share similar molecular characteristics and survival outcomes, suggesting that they should be considered as distinct molecular disease entities.
Article
Multidisciplinary Sciences
Wen Hao Neo, Yiran Meng, Alba Rodriguez-Meira, Muhammad Z. H. Fadlullah, Christopher A. G. Booth, Emanuele Azzoni, Supat Thongjuea, Marella F. T. R. de Bruijn, Sten Eirik W. Jacobsen, Adam J. Mead, Georges Lacaud
Summary: The study reveals the crucial role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE. Loss of EZH2 activity in HE leads to the generation of non-functional EMPs due to a lack of Wnt signaling downregulation, while the generation of primitive erythroid cells is not affected. EZH2 is essential for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but becomes dispensable later on.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Guadalupe Onate, Alex Bataller, Ana Garrido, Montserrat Hoyos, Montserrat Arnan, Susana Vives, Rosa Coll, Mar Tormo, Antonia Sampol, Lourdes Escoda, Olga Salamero, Antoni Garcia, Joan Bargay, Alba Aljarilla, Josep F. Nomdedeu, Jordi Esteve, Jorge Sierra, Marta Pratcorona
Summary: This study analyzed the impact of DNMT3A(mut) in FLT3-ITD subsets and found that DNMT3A(mut) did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1, despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.
Review
Oncology
Oscar Molina, Alex Bataller, Namitha Thampi, Jordi Ribera, Isabel Granada, Pablo Velasco, Jose Luis Fuster, Pablo Menendez
Summary: B-ALL with hypodiploidy with less than 40 chromosomes is a rare genetic abnormality associated with poor prognosis and survival rates in patients. Understanding the biological mechanisms involved in this subtype is crucial for improving patient outcomes.
Article
Hematology
Alex Bataller, Ana Garrido, Francesca Guijarro, Guadalupe Onate, Marina Diaz-Beya, Montserrat Arnan, Mar Tormo, Susana Vives, Maria Paz Queipo de Llano, Rosa Coll, David Gallardo, Ferran Vall-Llovera, Lourdes Escoda, Antonio Garcia-Guinon, Olga Salamero, Antonia Sampol, Brayan M. Merchan, Joan Bargay, Sandra Castano-Diez, Daniel Esteban, Aina Oliver-Caldes, Andrea Rivero, Pablo Mozas, Monica Lopez-Guerra, Marta Pratcorona, Lurdes Zamora, Dolors Costa, Maria Rozman, Josep F. Nomdedeu, Dolors Colomer, Salut Brunet, Jorge Sierra, Jordi Esteve
Summary: The 2017 European LeukemiaNet guidelines for acute myeloid leukemia have been validated in a large cohort of patients and identified a genetic subset with a very poor prognosis.
Article
Hematology
Clara Bueno, Susana Barrera, Alex Bataller, Valentin Ortiz-Maldonado, Natalina Elliot, Sorcha O'Byrne, Guanlin Wang, Montse Rovira, Francisco Gutierrez-Aguera, Juan L. Trincado, Maria Gonzalez-Gonzalez, Mireia Morgades, Marc Sorigue, Paloma Barcena, Samanta Romina Zanetti, Montse Torrebadell, Nerea Vega-Garcia, Susana Rives, Mar Mallo, Francesc Sole, Adam J. Mead, Irene Roberts, Supat Thongjuea, Bethan Psaila, Manel Juan, Julio Delgado, Alvaro Urbano-Ispizua, Josep Maria Ribera, Alberto Orfao, Anindita Roy, Pablo Menendez
Summary: CD19-directed immunotherapies have greatly improved the treatment of B-cell acute lymphoblastic leukemia (B-ALL). However, many patients still experience relapse. This study reveals the presence of pre-leukemic CD34(+)CD19(-)CD22(+) cells, which may contribute to phenotypic escape after CD19-directed immunotherapies.
Article
Biophysics
Francesca Guijarro, Alex Bataller, Marina Diaz-Beya, Ana Garrido, Christelle Coll-Ferra, Susana Vives, Olga Salamero, David Valcarcel, Mar Tormo, Montserrat Arnan, Antonia Sampol, Sandra Castano-Diez, Carmen Martinez, Maria Suarez-Lledo, Francesc Fernandez-Aviles, Juan Carlos Hernandez-Boluda, Josep Maria Ribera, Montserrat Rovira, Salut Brunet, Jorge Sierra, Jordi Esteve
Summary: This study analyzed the long-term outcomes of a sequential regimen based on IDA-FLAG and high-dose melphalan in patients with relapsed/refractory acute myeloid leukemia. The results showed that this regimen achieved a high complete response rate and a lower cumulative relapse incidence, but also had a high non-relapse mortality and a significant incidence of grade 3-4 acute graft-versus-host disease. Long-term survivors enjoyed a good quality of life.
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Mireia Ramos-Muntada, Juan L. Trincado, Joan Blanco, Clara Bueno, Virginia C. Rodriguez-Cortez, Alex Bataller, Belen Lopez-Millan, Claire Schwab, Margarita Ortega, Pablo Velasco, Maria L. Blanco, Josep Nomdedeu, Manuel Ramirez-Orellana, Alfredo Minguela, Jose L. Fuster, Esther Cuatrecasas, Mireia Camos, Paola Ballerini, Gabriele Escherich, Judith Boer, Monique DenBoer, Jesus M. Hernandez-Rivas, Maria J. Calasanz, Giovanni Cazzaniga, Christine J. Harrison, Pablo Menendez, Oscar Molina
Summary: The study reveals the presence of specific chromosomal gains and clonal heterogeneity in B-ALL, which are closely related to the clinical outcomes of patients. Additionally, distinct patterns of clonal evolution are observed at relapse. This study provides a reliable prognostic sub-stratification for pediatric B-ALL patients.
MOLECULAR ONCOLOGY
(2022)
Letter
Oncology
Alex Bataller, Fadi G. Haddad, Ghayas C. Issa, Koji Sasaki, Elias Jabbour, Gautam Borthakur, Alessandra Ferrajoli, Nicholas J. Short
LEUKEMIA & LYMPHOMA
(2023)
Article
Hematology
Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D. DiNardo, Naval Daver, Musa Yilmaz, Hussein A. Abbas, Nicholas J. Short, Ghayas Issa, Elias Jabbour, Sherry A. Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J. Shpall, Richard E. Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia
Summary: This study retrospectively evaluated the contemporary outcomes of older patients with acute myeloid leukemia (AML). The results showed that low-intensity therapy (LIT) and stem cell transplantation (SCT) have improved the treatment outcomes for this population. The study also identified common adverse clinical and cytogenetic findings in older AML patients. Measures should be taken to increase access to SCT for older AML patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Letter
Hematology
Emmanuel Almanza-Huante, Alex Bataller, Samuel Urrutia, Georgina Gener-Ricos, Robert Edward Briski, Rashmi Kanagal-Shamanna, Karen H. Lu, Shannon N. Westin, Timothy A. Yap, Koichi Takahashi, Farhad Ravandi, Yesid Alvarado, Tapan Kadia, Koiji Sasaki, Hagop M. Kantarjian, Guillermo Garcia-Manero
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Letter
Oncology
Samuel Urrutia, Ziyi Li, Emmanuel Almanza, Alex Bataller, Rashmi Kanagal-Shamanna, Jayastu Senapati, Koji Sasaki, Kelly Chien, Guillermo Montalban-Bravo, Courtney DiNardo, Gautam Borthakur, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Editorial Material
Oncology
Alex Bataller, Kelly S. Chien, Koji Sasaki, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Samuel Urrutia, Emmanuel Almanza-Huante, Georgina Gener-Ricos, Farhad Ravandi, Elias Jabbour, Tapan Kadia, Gautam Borthakur, Guillermo Garcia-Manero
Article
Oncology
Guadalupe Onate, Marta Pratcorona, Ana Garrido, Alicia Artigas-Baleri, Alex Bataller, Mar Tormo, Montserrat Arnan, Susana Vives, Rosa Coll, Olga Salamero, Ferran Vall-Llovera, Antonia Sampol, Antoni Garcia, Marta Cervera, Sara Garcia Avila, Joan Bargay, Xavier F. Ortin, Josep Nomdedeu, Jordi Esteve, Jorge Sierra
Summary: This study analyzed 227 patients with FLT3-mutated acute myeloid leukemia (AML) and found that the addition of midostaurin to treatment improved outcomes, especially in patients with NPM1 mutations.
BLOOD CANCER JOURNAL
(2023)
Article
Hematology
Tapan M. Kadia, Farhad Ravandi, Matteo Molica, Alex Bataller, Gautam Borthakur, Naval Daver, Elias Jabbour, Courtney D. Dinardo, Naveen Pemmaraju, Nitin Jain, Alessandra Ferrajoli, Musa Ylimaz, Prithviraj Bose, Rebecca Slack Tidwell, Kayleigh R. Marx, Caitlin R. Rausch, Rashmi Kanagal-Shamanna, Sa Wang, Rabiul Islam, Richard Champlin, Elizabeth Shpall, Marina Konopleva, Guillermo Garcia-Manero, Hagop Kantarjian
Summary: The addition of cladribine or sorafenib to standard chemotherapy has improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). The combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) showed high rates of complete remission in AML patients, with even better results when sorafenib was added in patients with FLT3-ITD mutated AML.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Letter
Hematology
Samuel Urrutia, Kelly S. S. Chien, Ziyi Li, Alex Bataller, Emmanuel Almanza, Koji Sasaki, Guillermo Montalban-Bravo, Nicholas J. J. Short, Elias Jabbour, Tapan M. M. Kadia, Farhad Ravandi, Gautam Borthakur, Yesid Alvarado, Naval Daver, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Sherry A. A. Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Alex Bataller, Sanam Loghavi, Yoheved Gerstein, Alexandre Bazinet, Koji Sasaki, Kelly S. Chien, Danielle Hammond, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas Short, Ghayas C. Issa, Tapan M. Kadia, Naval Daver, Guilin Tang, Andres Quesada, Keyur P. Patel, Farhad Ravandi, Warren Fiskus, Cristopher P. Mill, Hagop M. Kantarjian, Kapil Bhalla, Guillermo Garcia-Manero, Betul Oran, Courtney D. Dinardo
Summary: DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In a study of 3795 patients, 4% had DDX41 variants and were diagnosed with AML (n=96), MDS (n=52), or chronic myelomonocytic leukemia (n=3). The most common DDX41 variants were p.R525H, p.M1I, and p.D140fs. Treatment-naïve patients with DDX41 variants had a high overall response rate, and the median overall survival was 49 months for AML and 71 months for MDS.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
