Article
Oncology
Jad Othman, Nicola Potter, Katya Mokretar, David Taussig, Anjum Khan, Pramila Krishnamurthy, Anne-Louise Latif, Paul Cahalin, James Aries, Mariam Amer, Edward Belsham, Eibhlin Conneally, Charles Craddock, Dominic Culligan, Mike Dennis, Caroline Duncan, Sylvie D. Freeman, Caroline Furness, Amanda Gilkes, Paraskevi Gkreka, Katherine Hodgson, Wendy Ingram, Manish Jain, Andrew King, Steven Knapper, Panagiotis Kottaridis, Mary Frances McMullin, Unmesh Mohite, Loretta Ngu, Jenny O'Nions, Katharine Patrick, Tom Rider, Wing Roberts, Marianne Tang Severinsen, Neill Storrar, Tom Taylor, Nigel H. Russell, Richard Dillon
Summary: Patients with FLT3-mutated AML are at high risk of relapse and poor outcomes. Monitoring measurable residual disease (MRD) can help identify patients destined to relapse, providing an opportunity for pre-emptive intervention. In this study, 56 patients with molecular failure were treated with FLT3 inhibitors (FLT3i), resulting in a molecular response rate of 60% and an overall survival rate of 80% at 2 years. High-sensitivity next-generation sequencing identified patients more likely to benefit from FLT3i monotherapy. Further prospective studies are warranted to evaluate this promising treatment strategy.
Article
Oncology
Anudishi Tyagi, Appalaraju Jaggupilli, Stanley Ly, Bin Yuan, Fouad El-Dana, Venkatesh L. Hegde, Vivek Anand, Bijender Kumar, Mamta Puppala, Zheng Yin, Stephen T. C. Wong, Alexis Mollard, Hariprasad Vankayalapati, Jason M. Foulks, Steven L. Warner, Naval Daver, Gautam Borthakur, V. Lokesh Battula
Summary: The study identified ACVR1 as a factor favoring AML growth and a potential therapeutic target. ACVR1 was found to be overexpressed in FLT3-mutated AML and inhibition of ACVR1 expression increased the sensitivity of AML cells to FLT3 inhibitors. A novel ACVR1 inhibitor, TP-0184, was developed and shown to selectively arrest the growth of FLT3-mutated AML cells.
Article
Oncology
Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Berard, Sarah Bertoli, Marie-Anne Hospital, Mael Heiblig, Yohann Desbrosses, Caroline Bonmati, Cecile Pautas, Juliette Lambert, Corentin Orvain, Anne Banos, Florence Pasquier, Pierre Peterlin, Tony Marchand, Madalina Uzunov, Jamile Frayfer, Pascal Turlure, Thomas Cluzeau, Eric Jourdan, Chantal Himberlin, Emmanuelle Tavernier, Alban Villate, Stephanie Haiat, Marie-Lorraine Chretien, Martin Carre, Sylvain Chantepie, Ioana Vaida, Mathieu Wemeau, Safia Chebrek, Gaelle Guillerm, Romain Guieze, Houria Debarri, Eve Gehlkopf, Kamel Laribi, Ambroise Marcais, Alberto Santagostino, Marie-Christine Bene, Ariane Mineur, Arnaud Pigneux, Herve Dombret, Christian Recher
Summary: The real-world efficacy and safety of gilteritinib were assessed in a study of 167 R/R FLT3-mutated AML patients. The results showed that gilteritinib had a similar response rate and overall survival compared to the ADMIRAL trial, providing new insights into patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
Review
Oncology
Nicholas J. Short, Daniel Nguyen, Farhad Ravandi
Summary: FLT3 is frequently mutated in acute myeloid leukemia, and FLT3 inhibitors have shown potential in treating the disease. However, their effectiveness in older patients is still uncertain. This population, who are unfit for intensive chemotherapy, represents an unmet need. Combining FLT3 inhibitors with venetoclax, a commonly used treatment, may provide a new approach. Early results of incorporating FLT3 inhibitors into standard regimens for older patients with FLT3-mutated AML are promising.
BLOOD CANCER JOURNAL
(2023)
Article
Multidisciplinary Sciences
Tamara Castano-Bonilla, Juan M. Alonso-Dominguez, Eva Barragan, Rebeca Rodriguez-Veiga, Claudia Sargas, Cristina Gil, Carmen Chillon, Maria B. Vidriales, Raimundo Garcia, Joaquin Martinez-Lopez, Rosa Ayala, Maria J. Larrayoz, Eduardo Anguita, Rebeca Cuello, Alberto Cantalapiedra, Estrella Carrillo, Elena Soria-Saldise, Jorge Labrador, Isabel Recio, Lorenzo Algarra, Carlos Rodriguez-Medina, Cristina Bilbao-Syeiro, Juan A. Lopez-Lopez, Josefina Serrano, Erik De Cabo, Maria J. Sayas, Maria T. Olave, Joaquin Sanchez-Garcia, Mamen Mateos, Carlos Blas, Jose L. Lopez-Lorenzo, Daniel Lainez-Gonzalez, Juana Serrano, David Martinez-Cuadron, Miguel A. Sanz, Pau Montesinos
Summary: This study aimed to assess the prognostic impact of FLT3-ITD length and insertion site on complete remission rates, overall survival, and relapse-free survival of AML patients. The results suggest that FLT3-ITD length lacks prognostic value and clinical applicability.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Daelynn R. Buelow, Bhavana Bhatnagar, Shelley J. Orwick, Jae Yoon Jeon, Eric D. Eisenmann, Jack C. Stromatt, Navjot Singh Pabla, James S. Blachly, Sharyn D. Baker, Bradley W. Blaser
Summary: The study uncovered the mechanistic basis of resistance to gilteritinib, revealing common co-occurring mutations in RAS pathway genes among resistant patients. The BMX kinase played a crucial role in resistance, and enhancing the effectiveness of gilteritinib could be achieved by inhibiting BMX.
Article
Hematology
Laura K. Schmalbrock, Anna Dolnik, Sibylle Cocciardi, Eric Straeng, Frauke Theis, Nikolaus Jahn, Ekaterina Panina, Tamara J. Blaette, Julia Herzig, Sabrina Skambraks, Frank G. Ruecker, Verena Gaidzik, Peter Paschka, Walter Fiedler, Helmut R. Salih, Gerald Wulf, Thomas Schroeder, Michael Luebbert, Richard F. Schlenk, Felicitas Thol, Michael Heuser, Richard A. Larson, Arnold Ganser, Hendrik G. Stunnenberg, Saverio Minucci, Richard M. Stone, Clara D. Bloomfield, Hartmut Doehner, Konstanze Doehner, Lars Bullinger
Summary: This study investigated clonal evolution and resistance mechanisms in FLT3-ITD-mutated AML patients treated with midostaurin, revealing that some patients acquired mutations in signaling pathways, such as MAPK, after becoming FLT3-ITD negative, while others showed no FLT3-ITD mutational changes, suggesting alternative resistance mechanisms or loss of midostaurin inhibitory activity due to inadequate drug levels.
Article
Oncology
Jiao Wei, Ai-Min Hui, Nitika
Summary: This article is a summary of biomarkers for FLT3 inhibitors in acute myeloid leukemia (AML) and alternative approaches to overcome resistance to current therapies. AML is a type of leukemia where FLT3 gene mutations are common, making it an attractive target for treatment. However, the current inhibitors face challenges due to multiple mutations in the FLT3 gene. Therefore, the identification of biomarkers and finding alternative approaches are important.
Article
Hematology
Hartmut Doehner, Daniela Weber, Julia Krzykalla, Walter Fiedler, Gerald Wulf, Helmut Salih, Michael Luebbert, Michael W. M. Kuehn, Thomas Schroeder, Hans Salwender, Katharina Goetze, Joerg Westermann, Lars Fransecky, Karin Mayer, Bernd Hertenstein, Mark Ringhoffer, Hans-Joachim Tischler, Sigrid Machherndl-Spandl, Anika Schrade, Peter Paschka, Verena Gaidzik, Frauke Theis, Felicitas Thol, Michael Heuser, Richard F. Schlenk, Lars Bullinger, Maral Saadati, Axel Benner, Richard Larson, Richard Stone, Konstanze Doehner, Arnold Ganser
Summary: This study evaluated the efficacy of midostaurin in combination with intensive chemotherapy, followed by allogeneic hematopoietic-cell transplantation (HCT) and a 1-year midostaurin maintenance therapy, in adult patients with acute myeloid leukemia (AML) and fms-related tyrosine kinase 3 (FLT3) internal tandem duplication (ITD). The results showed that adding midostaurin to intensive therapy significantly improved the outcome in both younger and older AML patients with FLT3-ITD.
Article
Oncology
Naval Daver, Sangeetha Venugopal, Farhad Ravandi
Summary: Approximately 30% of newly diagnosed AML patients have FLT3 gene mutations, with FLT3-ITDmut showing adverse prognostic impact. Guidelines recommend rapid molecular testing for FLT3(mut) and early use of targeted agents, but challenges remain in prolonged remission, limited options for refractory patients, and resistance mechanisms that call for multi-agent therapies.
BLOOD CANCER JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Szymon Milnerowicz, Julia Maszewska, Paulina Skowera, Magdalena Stelmach, Monika Lejman
Summary: Acute myeloid leukemia (AML) mainly affects elderly patients who are unfit for intensive chemotherapy. Researchers are exploring the combination of venetoclax and FLT3 inhibitors to overcome drug resistance in leukemic cells and improve treatment outcomes. The combination shows a synergistic effect and has the potential to enhance therapeutic approaches for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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.
Article
Biochemical Research Methods
Chaitanya Aluru, Mona Singh
Summary: The study introduces a reconciliation-based framework that considers the relative positions of protein domains within extant sequences to uncover tandem domain duplications accurately. By developing an integer linear programming approach and a heuristic algorithm, the researchers are able to identify single and tandem domain duplication events with high accuracy. Through extensive simulation studies and testing on an orthogroup with complex domain duplication patterns, the effectiveness of the approach is demonstrated.
Article
Oncology
Nikolaus Jahn, Ekaterina Jahn, Maral Saadati, Lars Bullinger, Richard A. Larson, Tiziana Ottone, Sergio Amadori, Thomas W. Prior, Joseph M. Brandwein, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S. Tallman, Gerhard Ehninger, Michael Heuser, Arnold Ganser, Celine Pallaud, Insa Gathmann, Julia Krzykalla, Axel Benner, Clara D. Bloomfield, Christian Thiede, Richard M. Stone, Hartmut Doehner, Konstanze Doehner
Summary: This study aimed to characterize the mutational landscape of FLT3-mutated AML patients treated with intensive chemotherapy plus midostaurin or placebo. The results showed that concurrent mutations with FLT3 mutation were most frequent in NPM1, DNMT3A, WT1, TET2, NRAS, RUNX1, PTPN11, and ASXL1 genes. The study also identified the prognostic impact of WT1 and NPM1 mutations, as well as the treatment effect of midostaurin.
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
Hematology
Yachiyo Kuwatsuka, Daisuke Tomizawa, Rika Kihara, Yasunobu Nagata, Norio Shiba, Yuka Iijima-Yamashita, Akira Shimada, Takao Deguchi, Hayato Miyachi, Akio Tawa, Takashi Taga, Akitoshi Kinoshita, Hideki Nakayama, Nobutaka Kiyokawa, Akiko Moriya Saito, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Yasushi Miyazaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Shinichi Kobayashi, Kunio Kitamura, Emiko Sakaida, Seishi Ogawa, Tomoki Naoe, Yasuhide Hayashi, Keizo Horibe, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Hitoshi Kiyoi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2018)
Article
Pharmacology & Pharmacy
Kenta Yagi, Akira Shimada, Toshiaki Sendo
EUROPEAN JOURNAL OF PHARMACOLOGY
(2018)
Article
Hematology
Chihiro Tomoyasu, Toshihiko Imamura, Toshihiro Tomii, Mio Yano, Daisuke Asai, Hiroaki Goto, Akira Shimada, Masashi Sanada, Shotaro Iwamoto, Junko Takita, Masayoshi Minegishi, Takeshi Inukai, Kanji Sugita, Hajime Hosoi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2018)
Article
Hematology
Akira Shimada, Yuka Iijima-Yamashita, Akio Tawa, Daisuke Tomizawa, Miho Yamada, Shiba Norio, Tomoyuki Watanabe, Takashi Taga, Shotaro Iwamoto, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Akiko Moriya Saito, Nobutaka Kiyokawa, Keizo Horibe, Yusuke Hara, Kentaro Oki, Yasuhide Hayashi, Shiro Tanaka, Souichi Adachi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2018)
Article
Hematology
M. Aoe, H. Ishida, T. Matsubara, S. Karakawa, H. Kawaguchi, K. Fujiwara, K. Kanamitsu, K. Washio, K. Okada, M. Shibakura, A. Shimada
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2018)
Article
Pediatrics
Hidemasa Matsuo, Yuka Iijima-Yamashita, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
PEDIATRICS INTERNATIONAL
(2018)
Article
Pediatrics
Yuka Iijima-Yamashita, Hidemasa Matsuo, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Hiroyuki Takahashi, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
PEDIATRICS INTERNATIONAL
(2018)
Article
Immunology
Takaki Asano, Satoshi Okada, Miyuki Tsumura, Tzu-Wen Yeh, Kanako Mitsui-Sekinaka, Yuki Tsujita, Youjiro Ichinose, Akira Shimada, Kunio Hashimoto, Taizo Wada, Kohsuke Imai, Osamu Ohara, Tomohiro Morio, Shigeaki Nonoyama, Masao Kobayashi
FRONTIERS IN IMMUNOLOGY
(2018)
Editorial Material
Pediatrics
Kazumasa Zensho, Hisashi Ishida, Hiroki Nagai, Hirokazu Tsukahara, Akira Shimada
PEDIATRICS INTERNATIONAL
(2018)
Editorial Material
Pediatrics
Hisashi Ishida, Ryoichi Araki, Takashi Iwase, Tomoko Naito, Akira Shimada
PEDIATRICS INTERNATIONAL
(2019)
Review
Rheumatology
Kaori Fujiwara, Junya Shimizu, Hirokazu Tsukahara, Akira Shimada
RHEUMATOLOGY INTERNATIONAL
(2019)
Article
Oncology
Daiichiro Hasegawa, Akio Tawa, Daisuke Tomizawa, Tomoyuki Watanabe, Akiko Moriya Saito, Kazuko Kudo, Takashi Taga, Shotaro Iwamoto, Akira Shimada, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Hayato Miyachi, Keizo Horibe, Tatsutoshi Nakahata, Souichi Adachi
PEDIATRIC BLOOD & CANCER
(2020)
Article
Medicine, Research & Experimental
Hisashi Ishida, Akihiro Iguchi, Michinori Aoe, Ritsuo Nishiuchi, Takehiro Matsubara, Dai Keino, Masashi Sanada, Akira Shimada
BIOMEDICAL REPORTS
(2020)
Article
Oncology
Yousuke Higuchi, Takayuki Motoki, Hisashi Ishida, Kiichiro Kanamitsu, Kana Washio, Takanori Oyama, Takuo Noda, Yasuko Tsurumaru, Ayumi Okada, Hirokazu Tsukahara, Akira Shimada
Article
Medicine, Research & Experimental
Yuka Iwasaki, Rituo Nishiuchi, Michinori Aoe, Takahide Takahashi, Hirokazu Watanabe, Chiho Tokorotani, Kiyoshi Kikkawa, Akira Shimada
ACTA MEDICA OKAYAMA
(2017)