Article
Pharmacology & Pharmacy
Fangfang Wang, Jingcao Huang, Tingting Guo, Yuhuan Zheng, Li Zhang, Dan Zhang, Fujue Wang, Duolan Naren, Yushan Cui, Xiaoyan Liu, Ying Qu, Hongmei Luo, Yan Yang, Haichen Wei, Yong Guo
Summary: The combination treatment of HHT with quizartinib has shown synergistic effects on inhibiting cell growth, inducing apoptosis, and prolonging survival in mice with FLT3-ITD AML, suggesting it as a promising therapeutic strategy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Cell & Tissue Engineering
Rutvij A. Khanolkar, Rehan M. Faridi, Megan Kinzel, Kareem Jamani, Mary L. Savoie, Mona Shafey, Faisal M. Khan, Jan Storek
Summary: In cytogenetically intermediate-risk AML patients undergoing HCT, the presence of FLT3 and NPM1 mutations does not appear to have prognostic value in predicting outcomes.
Article
Medicine, General & Internal
Harry P. Erba, Pau Montesinos, Hee-Je Kim, Elzbieta Patkowska, Radovan Vrhovac, Pavel Zak, Po -Nan Wang, Tsvetomir Mitov, James Hanyok, Yasser Mostafa Kamel, Jaime E. Connolly Rohrbach, Li Liu, Aziz Benzohra, Arnaud Lesegretain, Jorge Cortes, Alexander E. Perl, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Mark J. Levis, Richard F. Schlenk
Summary: The aim of the study was to compare the effect of Quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML. The results showed that the addition of Quizartinib to standard chemotherapy can improve overall survival in adult patients with FLT3-ITD-positive newly diagnosed AML.
Article
Oncology
Tim Grob, Mathijs A. Sanders, Christian M. Vonk, Francois G. Kavelaars, Melissa Rijken, Diana W. Hanekamp, Patrycja L. Gradowska, Jacqueline Cloos, Yngvar Floisand, Marinus van Marwijk Kooy, Markus G. Manz, Gert J. Ossenkoppele, Lidwine W. Tick, Violaine Havelange, Bob Lowenberg, Mojca Jongen-Lavrencic, Peter J. M. Valk
Summary: The study demonstrates that the next-generation sequencing-based detection of FLT3-ITD MRD predicts the risk of relapse and overall survival in patients with AML. The prognostic value of FLT3-ITD MRD exceeds that of other established clinical and molecular prognostic factors, highlighting its significance as a clinically relevant biomarker for dynamic disease risk assessment in AML.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
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.
Article
Multidisciplinary Sciences
Kun-Yin Qiu, Xiong-Yu Liao, Yong Liu, Ke Huang, Yang Li, Jian-Pei Fang, Dun-Hua Zhou
Summary: This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Zi-Yao Ou, Ke Wang, Wen-Wen Shen, Ge Deng, Ya-Yun Xu, Long-Fei Wang, Zhuo-Yan Zai, Yi-An Ling, Tao Zhang, Xiao-Qing Peng, Fei-Hu Chen
Summary: This study found that FLT3 internal tandem duplication mutation led to aberrant upregulation of E2F1 in acute myeloid leukemia (AML) patients. Knockdown of E2F1 inhibited cell proliferation and increased cell sensitivity to chemotherapy in FLT3-ITD-positive AML cells. FLT3-ITD promoted E2F1 expression and nuclear accumulation in AML cells, enhancing purine metabolism and supporting AML cell proliferation.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Sungyoung Lee, Choong-Hyun Sun, Heejun Jang, Daeyoon Kim, Sung-Soo Yoon, Youngil Koh, Seung Chan Na, Sung Im Cho, Man Jin Kim, Moon-Woo Seong, Ja Min Byun, Hongseok Yun
Summary: This study introduces a novel and efficient FLT3-ITD detection approach called ITDetect, which utilizes NGS data. ITDetect demonstrates higher accuracy and provides more detailed information compared to existing in silico methods. Validation experiments show that ITDetect has the highest concordance with experimental methods.
BMC BIOINFORMATICS
(2023)
Article
Oncology
Monica Hellesoy, Caroline Engen, Tim Grob, Bob Lowenberg, Peter J. M. Valk, Bjorn T. Gjertsen
Summary: The incidence, molecular presentation, and outcome of AML are influenced by sex, with significant molecular differences observed between female and male patients, including prevalence of co-occurring mutations in female AML. While FLT3-ITD mutations are overrepresented in female patients, males with FLT3-ITDs have additional mutations in RNA splicing and epigenetic modifier genes. Sex-specific considerations could improve prognostication, prediction, and therapeutic strategies in AML.
MOLECULAR ONCOLOGY
(2021)
Review
Biochemical Research Methods
Danyang Yuan, Xiaoyu He, Xinyin Han, Chunyan Yang, Fei Liu, Shuying Zhang, Haijing Luan, Ruilin Li, Jiayin He, Xiaohong Duan, Dongliang Wang, Qiming Zhou, Sujun Gao, Beifang Niu
Summary: This study provided a comprehensive review of the principles, functionality, and limitations of existing methods for detecting FLT3-ITD, comparing the qualitative and quantitative detection capabilities of six representative tools. The results offer practical guidance for researchers and clinicians in selecting appropriate FLT3-ITD detection tools and highlight future developments in this field.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Cell Biology
Sivasundaram Karnan, Ichiro Hanamura, Akinobu Ota, Souichi Takasugi, Ayano Nakamura, Miyuki Takahashi, Kaori Uchino, Satsuki Murakami, Md Wahiduzzaman, Lam Quang Vu, Md Lutfur Rahman, Muhammad Nazmul Hasan, Toshinori Hyodo, Hiroyuki Konishi, Shinobu Tsuzuki, Kazuhiro Yoshikawa, Susumu Suzuki, Ryuzo Ueda, Masayuki Ejiri, Yoshitaka Hosokawa, Akiyoshi Takami
Summary: STAT5 activation in genetically modified FLT3-ITD knock-in human myeloid leukemia K562 cells upregulates CD52 expression, while the anti-CD52 antibody alemtuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) and shows antitumor effects in FLT3(ITD/WT) cells.
CELL DEATH DISCOVERY
(2021)
Article
Oncology
Hiroto Inaba, Jolieke G. van Oosterwijk, John C. Panetta, Lie Li, Daelynn R. Buelow, James S. Blachly, Sheila Shurtleff, Ching-Hon Pui, Raul C. Ribeiro, Jeffrey E. Rubnitz, Stanley Pounds, Sharyn D. Baker
Summary: The combination therapy of crenolanib and sorafenib shows good efficacy and tolerability in FLT3-ITD positive AML, with rare emergence of FLT3-KD mutations.
CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Hematology
Sara E. Meyer
Summary: In this issue of Blood, Li et al.1 explore the role of FLT3 internal tandem duplication (ITD) in orchestrating transcriptional and epigenetic programs in myeloid progenitor cells, resulting in distinct functional outputs.
Article
Genetics & Heredity
Ratilal Akabari, Dahui Qin, Mohammad Hussaini
Summary: This study compares the performance of three commercial kits in detecting CEBPA and FLT3 mutations. The results show that all three kits have 100% sensitivity in detecting CEBPA and FLT3 mutations, and there is high concordance in detecting confirmed variants in core myeloid genes. These findings indicate that NGS assays can now reliably detect CEBPA and FLT3 mutations.
Letter
Hematology
Annalisa Ruggeri, Liesbeth C. de Wreede, Carlheinz R. Muller, Pietro Crivello, Edouard F. Bonneville, Effie W. Petersdorf, Gerard Socie, Valerie Dubois, Riitta Niittyvuopio, Juha Perasaari, Ibrahim Yakoub-Agha, Jan J. Cornelissen, Lotte Wieten, Tobias Gedde-Dahl, Edouard Forcade, Charles R. Crawley, Steven G. E. Marsh, Virginie Gandemer, Eleni Tholouli, Claude-Eric Bulabois, Anne Huynh, Goda Choi, Eric Deconinck, Maija Itala-Remes, Stig Lenhoff, Mats Bengtsson, Jan-Erik Johansson, Gwendolyn van Gorkom, Jorinde D. Hoogenboom, Luca Vago, Vanderson Rocha, Chiara Bonini, Christian Chabannon, Katharina Fleischhauer
Letter
Hematology
Michele Wieczorek, Myriam Labopin, Luca Castagna, Eolia Brissot, Gerard Socie, Anna Maria Raiola, Emanuele Angelucci, Arancha Bermudez Rodriguez, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Charles Crawley, Jean Baptiste Mear, Maurizio Musso, Renato Fanin, Daniele Avenoso, Pascal Turlure, Cristina Tecchio, Jaime Sanz, Fabio Ciceri, Arnon Nagler, Mohamad Mohty
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Sebastian Giebel, Myriam Labopin, Thomas Schroeder, Ryszard Swoboda, Johan Maertens, Jean Henri Bourhis, Giovanni Grillo, Urpu Salmenniemi, Inken Hilgendorf, Nicolaus Kroeger, Xavier Poire, Jan J. Cornelissen, Mutlu Arat, Bipin Savani, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
Summary: A comparison was made between two myeloablative regimens for acute myeloid leukemia (AML) patients, one involving cyclophosphamide and total body irradiation (CyTBI12Gy) and the other involving fludarabine and total body irradiation (FluTBI12Gy). The results showed that the two regimens had similar efficacy in terms of relapse rate, non-relapse mortality, and survival rate. However, the FluTBI12Gy regimen was associated with a lower incidence of acute graft-versus-host disease and better survival rates.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Editorial Material
Hematology
Jean-Luc Harousseau, Mohamad Mohty
Article
Hematology
Anais Schavgoulidze, Alexis Talbot, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Salomon Manier, Laure Buisson, Sabrina Maheo, Laura Do Souto Ferreira, Luka Pavageau, Cyrille Hulin, Jean-Pierre Marolleau, Laurent Voillat, Karim Belhadj, Marion Divoux, Borhane Slama, Sabine Brechignac, Margaret Macro, Anne-Marie Stoppa, Laurence Sanhes, Frederique Orsini-Piocelle, Jean Fontan, Marie-Lorraine Chretien, Helene Demarquette, Mohamad Mohty, Herve Avet-Loiseau, Jill Corre
Summary: Our study aimed to confirm the adverse effect of 1p32 deletion in patients with newly diagnosed multiple myeloma (NDMM). We found that patients with del(1p32) had significantly inferior overall survival and progression-free survival compared to those without del(1p32). Biallelic del(1p32) conferred a dramatically poorer prognosis than monoallelic del(1p32).
Review
Biophysics
Mohamad Mohty, Florent Malard, Ahmed S. Alaskar, Mahmoud Aljurf, Mutlu Arat, Peter Bader, Frederic Baron, Ali Bazarbachi, Didier Blaise, Eolia Brissot, Fabio Ciceri, Selim Corbacioglu, Jean-Hugues Dalle, Fiona Dignan, Anne Huynh, Michelle Kenyon, Arnon Nagler, Antonio Pagliuca, Zinaida Peric, Paul G. Richardson, Annalisa Ruggeri, Tapani Ruutu, Ibrahim Yakoub-Agha, Rafael F. Duarte, Enric Carreras
Summary: Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can occur after hematopoietic cell transplantation (HCT). The European Society for Blood and Marrow Transplantation (EBMT) has recently updated the definition and severity grading system for SOS/VOD in adult patients. The aim of this work is to provide an update on the diagnosis, severity assessment, pathophysiology, and treatment of SOS/VOD in adult patients.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Gesine Bug, Myriam Labopin, Riitta Niittyvuopio, Matthias Stelljes, Hans Christian Reinhardt, Inken Hilgendorf, Nicolaus Kroeger, Ain Kaare, Wolfgang Bethge, Kerstin Schaefer-Eckart, Mareike Verbeek, Stephan Mielke, Kristina Carlson, Ali Bazarbachi, Alexandros Spyridonidis, Bipin N. Savani, Arnon Nagler, Mohamad Mohty
Summary: Retrospective analysis compared two different conditioning regimens for AML patients undergoing HSCT and found that using FluTBI resulted in lower relapse probability but higher non-relapse mortality. There were no significant differences in overall survival and GRFS between the two groups. Therefore, FluTBI may be more suitable for younger patients below the age of 55.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Klaus Hirschbuehl, Myriam Labopin, Emmanuelle Polge, Didier Blaise, Jean Henri Bourhis, Gerard Socie, Edouard Forcade, Ibrahim Yakoub-Agha, Helene Labussiere-Wallet, Wolfgang Bethge, Patrice Chevallier, Sarah Bonnet, Matthias Stelljes, Alexandros Spyridonidis, Zinaida Peric, Eolia Brissot, Bipin Savani, Sebastian Giebel, Christoph Schmid, Fabio Ciceri, Arnon Nagler, Mohamad Mohty
Summary: Allogeneic hematopoietic cell transplantation is a curative treatment for high-risk acute lymphoblastic leukemia, and conditioning regimens based on 12 Gray total body irradiation are the standard for patients under 45 years old. However, elderly patients often receive intermediate intensity conditioning to reduce toxicity. A retrospective study compared the outcomes of different conditioning regimens in ALL patients over 45 years old.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Iman Abou Dalle, Myriam Labopin, Nicolaus Kroeger, Thomas Schroeder, Juergen Finke, Matthias Stelljes, Andreas Neubauer, Didier Blaise, Ibrahim Yakoub-Agha, Urpu Salmenniemi, Edouard Forcade, Maija Itala-Remes, Peter Dreger, Gesine Bug, Jakob Passweg, Michael Heuser, Goda Choi, Eolia Brissot, Sebastian Giebel, Arnon Nagler, Fabio Ciceri, Ali Bazarbachi, Mohamad Mohty
Summary: Pre-transplant detectable measurable residual disease (MRD) is still associated with high risk of relapse and poor outcomes in acute myeloid leukemia (AML). The impact of disease burden on prediction of relapse and survival in patients receiving allogeneic hematopoietic cell transplantation (allo-HCT) in first remission (CR1) was evaluated. The study found that patients in CR1 and MRD positive at time of transplant could still be salvaged by allo-HCT, with significantly better outcomes than patients transplanted with active disease.
BONE MARROW TRANSPLANTATION
(2023)
Review
Immunology
Mohammad Hassan Hodroj, Iman Abou Dalle, Nour Moukalled, Jean El Cheikh, Mohamad Mohty, Ali Bazarbachi
Summary: The outcome of B-cell acute lymphoblastic leukemia has improved with multi-agent chemotherapy and immunotherapeutic agents. However, relapse post-transplant is still common. This review discusses strategies such as tyrosine kinase inhibitors, innovative agents, and cellular therapy to prevent and overcome relapse post allo-HCT in ALL patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Stephan A. Grupp, Selim Corbacioglu, Hyoung Jin Kang, Takanori Teshima, Seong Lin Khaw, Franco Locatelli, Johan Maertens, Matthias Stelljes, Polina Stepensky, Paty Lopez, Vian Amber, Antonio Pagliuca, Paul G. Richardson, Mohamad Mohty
Summary: This study compared defibrotide prophylaxis plus best supportive care to best supportive care alone for preventing sinusoidal obstruction syndrome after hematopoietic stem-cell transplantation. The results showed that defibrotide did not provide a benefit in preventing sinusoidal obstruction syndrome.
LANCET HAEMATOLOGY
(2023)
Article
Medicine, General & Internal
Florent Malard, Ernst Holler, Brenda M. Sandmaier, He Huang, Mohamad Mohty
Summary: Acute graft-versus-host disease (GVHD) is a common immune complication that can occur after allogeneic haematopoietic cell transplantation (alloHCT). This Primer summarizes the epidemiology, pathophysiology, diagnosis, prevention and treatment of this disorder. The article also reviews future research avenues and the effect this disorder has on patients' quality of life.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Hematology
Molly C. Tokaz, Helen Baldomero, Andrew J. Cowan, Wael Saber, Hildegard Greinix, Mickey B. C. Koh, Nicolaus Kroeger, Mohamad Mohty, Sebastian Galeano, Shinichiro Okamoto, Naeem Chaudhri, Amado J. Karduss, Fabio Ciceri, Vergilio Antonio R. Colturato, Selim Corbacioglu, Alaa Elhaddad, Lisa M. Force, Cristobal Frutos, Andres Gomez-De Leon, Nada Hamad, Nelson Hamerschlak, Naya He, Aloysius Ho, Xiao-jun Huang, Ben Jacobs, Hee-Je Kim, Minako Iida, Leslie Lehmann, Regis Peffault de Latour, Mary-Elizabeth M. Percival, Martina Perdomo, Walid Rasheed, Kirk R. Schultz, Adriana Seber, Bor-Sheng Ko, Anderson Joao Simione, Alok Srivastava, Jeff Szer, William A. Wood, Yoshihisa Kodera, Arnon Nagler, John A. Snowden, Daniel Weisdorf, Jakob Passweg, Marcelo C. Pasquini, Anna Sureda, Yoshiko Atsuta, Mahmoud Aljurf, Dietger Niederwieser
Summary: Acute myeloid leukemia (AML) is a fast-progressing and historically challenging disease. Hematopoietic stem cell transplantation (HSCT) is the best treatment option for many patients, but access and utilization on a global scale are unclear. This study aimed to investigate the global use of HSCT in AML and identify areas of need. The study found that AML incidence has increased globally, as has the use of HSCT, particularly allogeneic HSCT. However, there are significant regional variations in HSCT utilization and practices, including differences in graft sources. Further research is needed to understand and address these disparities.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Thomas G. Martin, Marcelo Capra, Mohamad Mohty, Kenshi Suzuki, Hang Quach, Michele Cavo, Philippe Moreau, Meletios Dimopoulos, Kwee Yong, Christina Tekle, Meredith C. Foster, Yvonne Barnes, Marie-Laure Risse, Joseph Mikhael
Summary: The role, timing, and impact of transplantation on further therapy after relapse in multiple myeloma (MM) are still being debated in the era of highly active novel agents. The impact of prior transplantation on treatment benefit from monoclonal antibodies in patients with relapsed/refractory MM (RRMM) is largely unknown. This subgroup analysis examined efficacy and safety in patients from the Phase 3 IKEMA study with and without previous transplantation.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Medicine, Research & Experimental
Vincent Jachiet, Laure Ricard, Pierre Hirsch, Florent Malard, Laurent Pascal, Odile Beyne-Rauzy, Pierre Peterlin, Alexandre Thibault Jacques Maria, Norbert Vey, Maud D'Aveni, Marie-Pierre Gourin, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Louis Terriou, Benoit De Renzis, Eric Durot, Shanti Natarajan-Ame, Anne Vekhoff, Laurent Voillat, Sophie Park, Julien Vinit, Celine Dieval, Azeddine Dellal, Vincent Grobost, Lise Willems, Julien Rossignol, Eric Solary, Olivier Kosmider, Nicolas Dulphy, Lin Pierre Zhao, Lionel Ades, Pierre Fenaux, Olivier Fain, Mohamad Mohty, Beatrice Gaugler, Arsene Mekinian
Summary: Background systemic inflammatory and autoimmune diseases (SIADs) occur in a significant proportion of myelodysplastic syndrome (MDS) patients. The recently identified VEXAS syndrome, associated with somatic mutations in UBA1, is characterized by severe inflammatory conditions and hematological abnormalities, including MDS. However, the mechanisms underlying the association between MDS and SIADs are largely unknown. This study aimed to evaluate myeloid immune cell subsets in MDS patients with and without SIAD and compare them to healthy controls.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
