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314 results on '"Famulare, Christopher"'

1. Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia

Author

McCarter, Joseph G. W., Nemirovsky, David, Famulare, Christopher A., Farnoud, Noushin, Mohanty, Abhinita S., Stone-Molloy, Zoe S., Chervin, Jordan, Ball, Brian J., Epstein-Peterson, Zachary D., Arcila, Maria E., Stonestrom, Aaron J., Dunbar, Andrew, Cai, Sheng F., Glass, Jacob L., Geyer, Mark B., Rampal, Raajit K., Berman, Ellin, Abdel-Wahab, Omar I., Stein, Eytan M., Tallman, Martin S., Levine, Ross L., Goldberg, Aaron D., Papaemmanuil, Elli, Zhang, Yanming, Roshal, Mikhail, Derkach, Andriy, and Xiao, Wenbin

Published
2023
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2. Single-cell mutation analysis of clonal evolution in myeloid malignancies

Author

Miles, Linde A, Bowman, Robert L, Merlinsky, Tiffany R, Csete, Isabelle S, Ooi, Aik T, Durruthy-Durruthy, Robert, Bowman, Michael, Famulare, Christopher, Patel, Minal A, Mendez, Pedro, Ainali, Chrysanthi, Demaree, Benjamin, Delley, Cyrille L, Abate, Adam R, Manivannan, Manimozhi, Sahu, Sombeet, Goldberg, Aaron D, Bolton, Kelly L, Zehir, Ahmet, Rampal, Raajit, Carroll, Martin P, Meyer, Sara E, Viny, Aaron D, and Levine, Ross L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Biotechnology, Rare Diseases, Genetics, Clinical Research, Hematology, Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Cell Separation, Clone Cells, DNA Mutational Analysis, Humans, Immunophenotyping, Mutation, Myeloproliferative Disorders, Single-Cell Analysis, General Science & Technology
Abstract

Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later1-3. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.

Published
2020

3. Mutant and Wild-Type Isocitrate Dehydrogenase 1 Share Enhancing Mechanisms Involving Distinct Tyrosine Kinase Cascades in Cancer

Author

Chen, Dong, Xia, Siyuan, Wang, Mei, Lin, Ruiting, Li, Yuancheng, Mao, Hui, Aguiar, Mike, Famulare, Christopher A, Shih, Alan H, Brennan, Cameron W, Gao, Xue, Pan, Yaozhu, Liu, Shuangping, Fan, Jun, Jin, Lingtao, Song, Lina, Zhou, An, Mukherjee, Joydeep, Pieper, Russell O, Mishra, Ashutosh, Peng, Junmin, Arellano, Martha, Blum, William G, Lonial, Sagar, Boggon, Titus J, Levine, Ross L, and Chen, Jing

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Brain Disorders, Hematology, Rare Diseases, Cancer, Brain Cancer, Cell Line, Tumor, Disease Management, Humans, Isocitrate Dehydrogenase, Janus Kinase 2, Models, Biological, Mutation, NADP, Neoplasms, Phosphorylation, Protein Binding, Protein Multimerization, Protein-Tyrosine Kinases, fms-Like Tyrosine Kinase 3, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Isocitrate dehydrogenase 1 (IDH1) is important for reductive carboxylation in cancer cells, and the IDH1 R132H mutation plays a pathogenic role in cancers including acute myeloid leukemia (AML). However, the regulatory mechanisms modulating mutant and/or wild-type (WT) IDH1 function remain unknown. Here, we show that two groups of tyrosine kinases (TK) enhance the activation of mutant and WT IDH1 through preferential Y42 or Y391 phosphorylation. Mechanistically, Y42 phosphorylation occurs in IDH1 monomers, which promotes dimer formation with enhanced substrate (isocitrate or α-ketoglutarate) binding, whereas Y42-phosphorylated dimers show attenuated disruption to monomers. Y391 phosphorylation occurs in both monomeric and dimeric IDH1, which enhances cofactor (NADP+ or NADPH) binding. Diverse oncogenic TKs phosphorylate IDH1 WT at Y42 and activate Src to phosphorylate IDH1 at Y391, which contributes to reductive carboxylation and tumor growth, whereas FLT3 or the FLT3-ITD mutation activates JAK2 to enhance mutant IDH1 activity through phosphorylation of Y391 and Y42, respectively, in AML cells. SIGNIFICANCE: We demonstrated an intrinsic connection between oncogenic TKs and activation of WT and mutant IDH1, which involves distinct TK cascades in related cancers. In particular, these results provide an additional rationale supporting the combination of FLT3 and mutant IDH1 inhibitors as a promising clinical treatment of mutant IDH1-positive AML.See related commentary by Horton and Huntly, p. 699.This article is highlighted in the In This Issue feature, p. 681.

Published
2019

4. TP53 Y220C mutations in patients with myeloid malignancies.

Author

Gener-Ricos, Georgina, Bewersdorf, Jan P., Loghavi, Sanam, Bataller, Alex, Goldberg, Aaron D., Sasaki, Koji, Famulare, Christopher, Takahashi, Koichi, Issa, Ghayas C., Borthakur, Gautam, Kadia, Tapan M., Short, Nicholas J., Senapati, Jayastu, Carter, Bing Z., Patel, Keyur P., Kantarjian, Hagop, Andreeff, Michael, Stein, Eytan M., and DiNardo, Courtney D.

Subjects
NUCLEOTIDE sequencing, SOMATIC mutation, CORPORATE directors, TUMOR suppressor proteins, TRANSCRIPTION factors, CHRONIC leukemia
Abstract

This letter to the editor discusses the prevalence and characteristics of TP53 Y220C mutations in patients with myeloid malignancies. The study found that these mutations were detected in 4.8% of patients with TP53 mutated myeloid neoplasms, most of whom had myelodysplastic syndromes or acute myeloid leukemia. The study also identified other co-occurring mutations. The authors suggest that targeted therapies may hold promise in improving outcomes for patients with this mutation, but further research is needed to address other TP53 mutations. [Extracted from the article]

Published
2024
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5. Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells

Author

Chen, Dong, Xia, Siyuan, Zhang, Rukang, Li, Yuancheng, Famulare, Christopher A., Fan, Hao, Wu, Rong, Wang, Mei, Zhu, Allen C., Elf, Shannon E., Su, Rui, Dong, Lei, Arellano, Martha, Blum, William G., Mao, Hui, Lonial, Sagar, Stock, Wendy, Odenike, Olatoyosi, Le Beau, Michelle, Boggon, Titus J., He, Chuan, Chen, Jianjun, Gao, Xue, Levine, Ross L., and Chen, Jing

Published
2021
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6. Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia

Author

Xiao, Wenbin, Chan, Alexander, Waarts, Michael R., Mishra, Tanmay, Liu, Ying, Cai, Sheng F., Yao, Jinjuan, Gao, Qi, Bowman, Robert L., Koche, Richard P., Csete, Isabelle S., DelGaudio, Nicole L., Derkach, Andriy, Baik, Jeeyeon, Yanis, Sophia, Famulare, Christopher A., Patel, Minal, Arcila, Maria E., Stahl, Maximilian, Rampal, Raajit K., Tallman, Martin S., Zhang, Yanming, Dogan, Ahmet, Goldberg, Aaron D., Roshal, Mikhail, and Levine, Ross L.

Published
2021
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7. Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML

Author

Stahl, Maximilian, Menghrajani, Kamal, Derkach, Andriy, Chan, Alexander, Xiao, Wenbin, Glass, Jacob, King, Amber C., Daniyan, Anthony F., Famulare, Christopher, Cuello, Bernadette M., Horvat, Troy Z., Abdel-Wahab, Omar, Levine, Ross L., Viny, Aaron D., Stein, Eytan M., Cai, Sheng F., Roshal, Mikhail, Tallman, Martin S., and Goldberg, Aaron D.

Published
2021
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11. Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis

Author

Tamari, Roni, Rapaport, Franck, Zhang, Nan, McNamara, Caroline, Kuykendall, Andrew, Sallman, David A., Komrokji, Rami, Arruda, Andrea, Najfeld, Vesna, Sandy, Lonette, Medina, Juan, Litvin, Rivka, Famulare, Christopher A., Patel, Minal A., Maloy, Molly, Castro-Malaspina, Hugo, Giralt, Sergio A., Weinberg, Rona S., Mascarenhas, John O., Mesa, Ruben, Rondelli, Damiano, Dueck, Amylou C., Levine, Ross L., Gupta, Vikas, Hoffman, Ronald, and Rampal, Raajit K.

Published
2019
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12. Acute myeloid leukemia with mixed phenotype is characterized by stemness transcriptomic signatures and limited lineage plasticity

Author

Galera, Pallavi, primary, Dilip, Deepika, additional, Derkach, Andriy, additional, Chan, Alexander, additional, Zhang, Yanming, additional, Persuad, Sonali, additional, Mishera, Tanmay, additional, Liu, Ying, additional, Famulare, Christopher, additional, Gao, Qi, additional, Mata, Douglas A., additional, Arcila, Maria, additional, Geyer, Mark B., additional, Stein, Eytan, additional, Dogan, Ahmet, additional, Levine, Ross L., additional, Roshal, Mikhail, additional, Glass, Jacob, additional, and Xiao, Wenbin, additional

Published
2023
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13. PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation

Author

Xiao, Wenbin, Bharadwaj, Maheetha, Levine, Max, Farnhoud, Noushin, Pastore, Friederike, Getta, Bartlomiej M., Hultquist, Anne, Famulare, Christopher, Medina, Juan S., Patel, Minal A., Gao, Qi, Lewis, Natasha, Pichardo, Janine, Baik, Jeeyeon, Shaffer, Brian, Giralt, Sergio, Rampal, Raajit, Devlin, Sean, Cimera, Robert, Zhang, Yanming, E. Arcila, Maria, Papaemmanuil, Elli, Levine, Ross L., and Roshal, Mikhail

Published
2018
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14. Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia

Author

Robinson, Troy M., primary, Bowman, Robert L., additional, Persaud, Sonali, additional, Liu, Ying, additional, Neigenfind, Rosemary, additional, Gao, Qi, additional, Zhang, Jingping, additional, Sun, Xiaotian, additional, Miles, Linde A., additional, Cai, Sheng F., additional, Sciambi, Adam, additional, Llanso, Aaron, additional, Famulare, Christopher, additional, Goldberg, Aaron, additional, Dogan, Ahmet, additional, Roshal, Mikhail, additional, Levine, Ross L., additional, and Xiao, Wenbin, additional

Published
2023
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15. Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations

Author

Intlekofer, Andrew M., Shih, Alan H., Wang, Bo, Nazir, Abbas, Rustenburg, Ariën S., Albanese, Steven K., Patel, Minal, Famulare, Christopher, Correa, Fabian M., Takemoto, Naofumi, Durani, Vidushi, Liu, Hui, Taylor, Justin, Farnoud, Noushin, Papaemmanuil, Elli, Cross, Justin R., Tallman, Martin S., Arcila, Maria E., Roshal, Mikhail, Petsko, Gregory A., Wu, Bin, Choe, Sung, Konteatis, Zenon D., Biller, Scott A., Chodera, John D., Thompson, Craig B., Levine, Ross L., and Stein, Eytan M.

Published
2018
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16. Data from Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition

Author

Cai, Sheng F., primary, Chu, S. Haihua, primary, Goldberg, Aaron D., primary, Parvin, Salma, primary, Koche, Richard P., primary, Glass, Jacob L., primary, Stein, Eytan M., primary, Tallman, Martin S., primary, Sen, Filiz, primary, Famulare, Christopher A., primary, Cusan, Monica, primary, Huang, Chun-Hao, primary, Chen, Chun-Wei, primary, Zou, Lihua, primary, Cordner, Keith B., primary, DelGaudio, Nicole L., primary, Durani, Vidushi, primary, Kini, Mitali, primary, Rex, Madison, primary, Tian, Helen S., primary, Zuber, Johannes, primary, Baslan, Timour, primary, Lowe, Scott W., primary, Rienhoff, Hugh Y., primary, Letai, Anthony, primary, Levine, Ross L., primary, and Armstrong, Scott A., primary

Published
2023
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17. Supplementary Table from LKB1/STK11 Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms

Author

Marinaccio, Christian, primary, Suraneni, Praveen, primary, Celik, Hamza, primary, Volk, Andrew, primary, Wen, Qiang Jeremy, primary, Ling, Te, primary, Bulic, Marinka, primary, Lasho, Terra, primary, Koche, Richard P., primary, Famulare, Christopher A., primary, Farnoud, Noushin, primary, Stein, Brady, primary, Schieber, Michael, primary, Gurbuxani, Sandeep, primary, Root, David E., primary, Younger, Scott T., primary, Hoffman, Ronald, primary, Gangat, Naseema, primary, Ntziachristos, Panagiotis, primary, Chandel, Navdeep S., primary, Levine, Ross L., primary, Rampal, Raajit K., primary, Challen, Grant A., primary, Tefferi, Ayalew, primary, and Crispino, John D., primary

Published
2023
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18. Supplementary Table 1 from Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition

Author

Cai, Sheng F., primary, Chu, S. Haihua, primary, Goldberg, Aaron D., primary, Parvin, Salma, primary, Koche, Richard P., primary, Glass, Jacob L., primary, Stein, Eytan M., primary, Tallman, Martin S., primary, Sen, Filiz, primary, Famulare, Christopher A., primary, Cusan, Monica, primary, Huang, Chun-Hao, primary, Chen, Chun-Wei, primary, Zou, Lihua, primary, Cordner, Keith B., primary, DelGaudio, Nicole L., primary, Durani, Vidushi, primary, Kini, Mitali, primary, Rex, Madison, primary, Tian, Helen S., primary, Zuber, Johannes, primary, Baslan, Timour, primary, Lowe, Scott W., primary, Rienhoff, Hugh Y., primary, Letai, Anthony, primary, Levine, Ross L., primary, and Armstrong, Scott A., primary

Published
2023
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19. Supplementary Figures from Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

Author

Harding, James J., primary, Lowery, Maeve A., primary, Shih, Alan H., primary, Schvartzman, Juan M., primary, Hou, Shengqi, primary, Famulare, Christopher, primary, Patel, Minal, primary, Roshal, Mikhail, primary, Do, Richard K., primary, Zehir, Ahmet, primary, You, Daoqi, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Tallman, Martin S., primary, Hyman, David M., primary, Reznik, Ed, primary, Finley, Lydia W.S., primary, Papaemmanuil, Elli, primary, Tosolini, Alessandra, primary, Frattini, Mark G., primary, MacBeth, Kyle J., primary, Liu, Guowen, primary, Fan, Bin, primary, Choe, Sung, primary, Wu, Bin, primary, Janjigian, Yelena Y., primary, Mellinghoff, Ingo K., primary, Diaz, Luis A., primary, Levine, Ross L., primary, Abou-Alfa, Ghassan K., primary, Stein, Eytan M., primary, and Intlekofer, Andrew M., primary

Published
2023
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20. Supplementary Table 2 from Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition

Author

Cai, Sheng F., primary, Chu, S. Haihua, primary, Goldberg, Aaron D., primary, Parvin, Salma, primary, Koche, Richard P., primary, Glass, Jacob L., primary, Stein, Eytan M., primary, Tallman, Martin S., primary, Sen, Filiz, primary, Famulare, Christopher A., primary, Cusan, Monica, primary, Huang, Chun-Hao, primary, Chen, Chun-Wei, primary, Zou, Lihua, primary, Cordner, Keith B., primary, DelGaudio, Nicole L., primary, Durani, Vidushi, primary, Kini, Mitali, primary, Rex, Madison, primary, Tian, Helen S., primary, Zuber, Johannes, primary, Baslan, Timour, primary, Lowe, Scott W., primary, Rienhoff, Hugh Y., primary, Letai, Anthony, primary, Levine, Ross L., primary, and Armstrong, Scott A., primary

Published
2023
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21. Supplementary Figure from LKB1/STK11 Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms

Author

Marinaccio, Christian, primary, Suraneni, Praveen, primary, Celik, Hamza, primary, Volk, Andrew, primary, Wen, Qiang Jeremy, primary, Ling, Te, primary, Bulic, Marinka, primary, Lasho, Terra, primary, Koche, Richard P., primary, Famulare, Christopher A., primary, Farnoud, Noushin, primary, Stein, Brady, primary, Schieber, Michael, primary, Gurbuxani, Sandeep, primary, Root, David E., primary, Younger, Scott T., primary, Hoffman, Ronald, primary, Gangat, Naseema, primary, Ntziachristos, Panagiotis, primary, Chandel, Navdeep S., primary, Levine, Ross L., primary, Rampal, Raajit K., primary, Challen, Grant A., primary, Tefferi, Ayalew, primary, and Crispino, John D., primary

Published
2023
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22. Supplementary Data from Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition

Author

Cai, Sheng F., primary, Chu, S. Haihua, primary, Goldberg, Aaron D., primary, Parvin, Salma, primary, Koche, Richard P., primary, Glass, Jacob L., primary, Stein, Eytan M., primary, Tallman, Martin S., primary, Sen, Filiz, primary, Famulare, Christopher A., primary, Cusan, Monica, primary, Huang, Chun-Hao, primary, Chen, Chun-Wei, primary, Zou, Lihua, primary, Cordner, Keith B., primary, DelGaudio, Nicole L., primary, Durani, Vidushi, primary, Kini, Mitali, primary, Rex, Madison, primary, Tian, Helen S., primary, Zuber, Johannes, primary, Baslan, Timour, primary, Lowe, Scott W., primary, Rienhoff, Hugh Y., primary, Letai, Anthony, primary, Levine, Ross L., primary, and Armstrong, Scott A., primary

Published
2023
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23. Data from LKB1/STK11 Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms

Author

Marinaccio, Christian, primary, Suraneni, Praveen, primary, Celik, Hamza, primary, Volk, Andrew, primary, Wen, Qiang Jeremy, primary, Ling, Te, primary, Bulic, Marinka, primary, Lasho, Terra, primary, Koche, Richard P., primary, Famulare, Christopher A., primary, Farnoud, Noushin, primary, Stein, Brady, primary, Schieber, Michael, primary, Gurbuxani, Sandeep, primary, Root, David E., primary, Younger, Scott T., primary, Hoffman, Ronald, primary, Gangat, Naseema, primary, Ntziachristos, Panagiotis, primary, Chandel, Navdeep S., primary, Levine, Ross L., primary, Rampal, Raajit K., primary, Challen, Grant A., primary, Tefferi, Ayalew, primary, and Crispino, John D., primary

Published
2023
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24. Supplementary Methods from Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

Author

Harding, James J., primary, Lowery, Maeve A., primary, Shih, Alan H., primary, Schvartzman, Juan M., primary, Hou, Shengqi, primary, Famulare, Christopher, primary, Patel, Minal, primary, Roshal, Mikhail, primary, Do, Richard K., primary, Zehir, Ahmet, primary, You, Daoqi, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Tallman, Martin S., primary, Hyman, David M., primary, Reznik, Ed, primary, Finley, Lydia W.S., primary, Papaemmanuil, Elli, primary, Tosolini, Alessandra, primary, Frattini, Mark G., primary, MacBeth, Kyle J., primary, Liu, Guowen, primary, Fan, Bin, primary, Choe, Sung, primary, Wu, Bin, primary, Janjigian, Yelena Y., primary, Mellinghoff, Ingo K., primary, Diaz, Luis A., primary, Levine, Ross L., primary, Abou-Alfa, Ghassan K., primary, Stein, Eytan M., primary, and Intlekofer, Andrew M., primary

Published
2023
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26. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Author

Minuesa, Gerard, Albanese, Steven K., Xie, Wei, Kazansky, Yaniv, Worroll, Daniel, Chow, Arthur, Schurer, Alexandra, Park, Sun-Mi, Rotsides, Christina Z., Taggart, James, Rizzi, Andrea, Naden, Levi N., Chou, Timothy, Gourkanti, Saroj, Cappel, Daniel, Passarelli, Maria C., Fairchild, Lauren, Adura, Carolina, Glickman, J. Fraser, Schulman, Jessica, Famulare, Christopher, Patel, Minal, Eibl, Joseph K., Ross, Gregory M., Bhattacharya, Shibani, Tan, Derek S., Leslie, Christina S., Beuming, Thijs, Patel, Dinshaw J., Goldgur, Yehuda, Chodera, John D., and Kharas, Michael G.

Published
2019
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27. Supplementary Data from Aurora Kinase A Inhibition Provides Clinical Benefit, Normalizes Megakaryocytes, and Reduces Bone Marrow Fibrosis in Patients with Myelofibrosis: A Phase I Trial

Author

Gangat, Naseema, primary, Marinaccio, Christian, primary, Swords, Ronan, primary, Watts, Justin M., primary, Gurbuxani, Sandeep, primary, Rademaker, Alfred, primary, Fought, Angela J., primary, Frankfurt, Olga, primary, Altman, Jessica K., primary, Wen, Qiang Jeremy, primary, Farnoud, Noushin, primary, Famulare, Christopher A., primary, Patel, Akshar, primary, Tapia, Roberto, primary, Vallapureddy, Rangit R., primary, Barath, Stephanie, primary, Graf, Amy, primary, Handlogten, Amy, primary, Zblewski, Darci, primary, Patnaik, Mrinal M., primary, Al-kali, Aref, primary, Dinh, Yvonne Trang, primary, Englund Prahl, Kristen, primary, Patel, Shradha, primary, Nobrega, Juan Carlos, primary, Tejera, Dalissa, primary, Thomassen, Amber, primary, Gao, Juehua, primary, Ji, Peng, primary, Rampal, Raajit K., primary, Giles, Francis J., primary, Tefferi, Ayalew, primary, Stein, Brady, primary, and Crispino, John D., primary

Published
2023
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28. The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells

Author

Vu, Ly P, Pickering, Brian F, Cheng, Yuanming, Zaccara, Sara, Nguyen, Diu, Minuesa, Gerard, Chou, Timothy, Chow, Arthur, Saletore, Yogesh, MacKay, Matthew, Schulman, Jessica, Famulare, Christopher, Patel, Minal, Klimek, Virginia M, Garrett-Bakelman, Francine E, Melnick, Ari, Carroll, Martin, Mason, Christopher E, Jaffrey, Samie R, and Kharas, Michael G

Subjects
Hematopoiesis -- Research, Embryonic stem cells -- Research, Cell differentiation -- Research, Apoptosis -- Research, Myelocytic leukemia -- Diagnosis -- Care and treatment -- Research, Nonlymphoid leukemia -- Diagnosis -- Care and treatment -- Research, Biological sciences, Health
Abstract

N[sup.6]-methyladenosine (m[sup.6]A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m[sup.6]A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m[sup.6]A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth. METTL3 mRNA and protein are expressed more abundantly in acute myeloid leukemia (AML) cells than in healthy HSPCs or other types of tumor cells. Furthermore, METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m[sup.6]A coupled with ribosome profiling reveals that m[sup.6]A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT, which contributes to the differentiation-promoting effects of METTL3 depletion. Overall, these results provide a rationale for the therapeutic targeting of METTL3 in myeloid leukemia., Author(s): Ly P Vu [1, 12]; Brian F Pickering [2, 12]; Yuanming Cheng [1, 12]; Sara Zaccara [2]; Diu Nguyen [1]; Gerard Minuesa [1]; Timothy Chou [1]; Arthur Chow [1]; [...]

Published
2017
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29. Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia: an appraisal of the new WHO and IC classifications and ELN risk stratification

Author

McCarter, Joseph GW., primary, Nemirovsky, David, additional, Famulare, Christopher A., additional, Farnoud, Noushin, additional, Mohanty, Abhinita S., additional, Stone-Molloy, Zoe S., additional, Chervin, Jordan, additional, Ball, Brian J., additional, Epstein-Peterson, Zachary D., additional, Arcila, Maria E., additional, Stonestrom, Aaron J., additional, Dunbar, Andrew, additional, Cai, Sheng F., additional, Glass, Jacob L., additional, Geyer, Mark B., additional, Rampal, Raajit K., additional, Berman, Ellin, additional, Abdel-Wahab, Omar I., additional, Stein, Eytan M., additional, Tallman, Martin S., additional, Levine, Ross L., additional, Goldberg, Aaron D., additional, Papaemmanuil, Elli, additional, Zhang, Yanming, additional, Roshal, Mikhail, additional, Derkach, Andriy, additional, and Xiao, Wenbin, additional

Published
2022
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30. Safety and efficacy of CPX-351 in younger patients (< 60 years) with secondary acute myeloid leukemia

Author

Przespolewski, Amanda, primary, Goldberg, Aaron D, additional, Talati, Chetasi, additional, Fazal, Salman, additional, Vachhani, Pankit, additional, Sanikommu, Srinivasa Reddy, additional, Thota, Swapna, additional, Waksal, Julian A., additional, Ball, Brian John, additional, Famulare, Christopher A, additional, Stahl, Maximilian, additional, Baron, Jeffrey, additional, Griffiths, Elizabeth A, additional, Thompson, James E., additional, Sweet, Kendra L, additional, and Wang, Eunice S., additional

Published
2022
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31. Whole Genome Sequencing Comparison of Acute Myeloid Leukemia at Presentation and Remission Predicts Patient Outcome

Author

Moffitt, Andrea B, primary, Alexander, Joan, additional, Stepansky, Asya, additional, Famulare, Christopher, additional, Lopez, Carlos A, additional, Hakim, Nausheen, additional, Wu, Vernon, additional, Wang, Zihua, additional, Kolitz, Jonathan E., additional, Chiorazzi, Nicholas, additional, Allen, Steven L, additional, Levine, Ross L., additional, Levy, Dan, additional, and Wigler, Michael, additional

Published
2022
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32. Erythroid and Megakaryocytic Differentiation Program in JAK2-Mutated Acute Myeloid Leukemia with or without Antecedent Myeloproliferative Neoplasm

Author

Liu, Ying, primary, Sethi, Shenon, additional, Koche, Richard, additional, Gao, Qi, additional, Dilip, Deepika, additional, Glass, Jacob L, additional, Galera, Pallavi K, additional, Persaud, Sonali, additional, Mishra, Tanmay, additional, Sun, Xiaotian, additional, Londono, Dory, additional, Cimera, Robert, additional, Zhu, Menglei, additional, Famulare, Christopher, additional, Baik, Jeeyeon, additional, Bhurtel, Himanshu, additional, Arcila, Maria E., additional, Dogan, Ahmet, additional, Levine, Ross L., additional, Zhang, Yanming, additional, Roshal, Mikhail, additional, Rampal, Raajit K, additional, and Xiao, Wenbin, additional

Published
2022
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33. Single Cell Genotypic and Phenotypic Analysis of Measurable Residual Disease in Acute Myeloid Leukemia

Author

Robinson, Troy, primary, Bowman, Robert L., additional, Persaud, Sonali, additional, Liu, Ying, additional, Gao, Qi, additional, Zhang, Jing-Ping, additional, Sun, Xiaotian, additional, Sciambi, Adam, additional, Llanso, Aaron, additional, Famulare, Christopher, additional, Goldberg, Aaron D, additional, Dogan, Ahmet, additional, Roshal, Mikhail, additional, Levine, Ross L., additional, and Xiao, Wenbin, additional

Published
2022
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34. Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia

Author

Stahl, Maximilian, primary, Derkach, Andriy, additional, Farnoud, Noushin, additional, Bewersdorf, Jan Philipp, additional, Robinson, Troy, additional, Famulare, Christopher, additional, Cho, Christina, additional, Devlin, Sean, additional, Menghrajani, Kamal, additional, Patel, Minal A., additional, Cai, Sheng F., additional, Miles, Linde A., additional, Bowman, Robert L., additional, Geyer, Mark B., additional, Dunbar, Andrew, additional, Epstein‐Peterson, Zachary D., additional, McGovern, Erin, additional, Schulman, Jessica, additional, Glass, Jacob L., additional, Taylor, Justin, additional, Viny, Aaron D., additional, Stein, Eytan M., additional, Getta, Bartlomiej, additional, Arcila, Maria E., additional, Gao, Qi, additional, Barker, Juliet, additional, Shaffer, Brian C., additional, Papadopoulos, Esperanza B., additional, Gyurkocza, Boglarka, additional, Perales, Miguel‐Angel, additional, Abdel‐Wahab, Omar, additional, Levine, Ross L., additional, Giralt, Sergio A., additional, Zhang, Yanming, additional, Xiao, Wenbin, additional, Pai, Nidhi, additional, Papaemmanuil, Elli, additional, Tallman, Martin S., additional, Roshal, Mikhail, additional, and Goldberg, Aaron D., additional

Published
2022
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35. Safety and efficacy of CPX-351 in younger patients (

Author

Przespolewski, Amanda, Goldberg, Aaron D., Talati, Chetasi, Fazal, Salman, Vachhani, Pankit, Sanikommu, Srinivasa R., Thota, Swapna, Waksal, Julian, Ball, Brian, Famulare, Christopher, Stahl, Maximilian, Baron, Jeffrey, Griffiths, Elizabeth A., Thompson, James E., Sweet, Kendra, and Wang, Eunice S.

Published
2023
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36. Single cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia

Author

Robinson, Troy M., primary, Bowman, Robert L., additional, Persaud, Sonali, additional, Liu, Ying, additional, Gao, Qi, additional, Zhang, Jingping, additional, Sun, Xiaotian, additional, Miles, Linde A., additional, Cai, Sheng F., additional, Sciambi, Adam, additional, Llanso, Aaron, additional, Famulare, Christopher, additional, Goldberg, Aaron, additional, Dogan, Ahmet, additional, Roshal, Mikhail, additional, Levine, Ross L., additional, and Xiao, Wenbin, additional

Published
2022
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37. Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia.

Author

Stahl, Maximilian, Derkach, Andriy, Farnoud, Noushin, Bewersdorf, Jan Philipp, Robinson, Troy, Famulare, Christopher, Cho, Christina, Devlin, Sean, Menghrajani, Kamal, Patel, Minal A., Cai, Sheng F., Miles, Linde A., Bowman, Robert L., Geyer, Mark B., Dunbar, Andrew, Epstein‐Peterson, Zachary D., McGovern, Erin, Schulman, Jessica, Glass, Jacob L., and Taylor, Justin

Published
2023
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38. Clinical and Genomic Characterization of Secondary Acute Myeloid Leukemia with Mixed Phenotype

Author

Galera, Pallavi, primary, Chan, Alexander, additional, Derkach, Andriy, additional, Liu, Ying, additional, Baik, Jeeyeon, additional, Famulare, Christopher, additional, Sigler, Allison, additional, Arcila, Maria E., additional, Mata, Douglas A, additional, Dogan, Ahmet, additional, Tallman, Martin S., additional, Levine, Ross L., additional, Zhang, Yanming, additional, Roshal, Mikhail, additional, Glass, Jacob L, additional, and Xiao, Wenbin, additional

Published
2021
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39. Chemotherapy-Related Mutational Signatures Reveal the Origins of Therapy-Related Myeloid Neoplasms

Author

Diamond, Benjamin, primary, Ziccheddu, Bachisio, additional, Boyle, Eileen M, additional, Maclachlan, Kylee H, additional, Arango Ossa, Juan, additional, Taylor, Justin, additional, Watts, Justin, additional, Lu, Sydney X., additional, Yellapantula, Venkata D, additional, Famulare, Christopher, additional, Chojnacka, Monika, additional, Rajanna, Arjun Raj, additional, Mason, Emilia, additional, Coffey, David G., additional, Hoffman, James E., additional, Kazandjian, Dickran, additional, Bradley, Terrence J, additional, Zhu, Menglei, additional, Bolli, Niccolo, additional, Papaemmanuil, Elli, additional, Bolton, Kelly L., additional, Scordo, Michael, additional, Lahoud, Oscar B, additional, Stein, Eytan M., additional, Sauter, Craig S., additional, Hassoun, Hani, additional, Mailankody, Sham, additional, Korde, Neha, additional, Hultcrantz, Malin, additional, Shah, Urvi A, additional, Shah, Gunjan L, additional, Park, Jae H, additional, Landau, Heather J, additional, Ganesh, Karuna, additional, Sekeres, Mikkael A., additional, Nimer, Stephen, additional, Chung, David J., additional, Ho, Caleb, additional, Roshal, Mikhail, additional, Lesokhin, Alexander, additional, Morgan, Gareth J., additional, Landgren, Ola, additional, and Maura, Francesco, additional

Published
2021
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40. Comparing Outcomes between Liposomal Daunorubicin/Cytarabine (CPX-351) and HMA+Venetoclax As Frontline Therapy in Acute Myeloid Leukemia

Author

Grenet, Justin, primary, Jain, Akriti G, additional, Burkart, Madelyn, additional, Waksal, Julian, additional, Famulare, Christopher, additional, Numan, Yazan, additional, Stahl, Maximilian, additional, Mckinnell, Zoe, additional, Ball, Brian, additional, Ma, Xiaoyue, additional, Christos, Paul J, additional, Ritchie, Ellen, additional, Samuel, Michael B., additional, Kaner, Justin D., additional, Lee, Sangmin, additional, Goldberg, Aaron D, additional, Dinner, Shira, additional, Sweet, Kendra, additional, Roboz, Gail J., additional, and Desai, Pinkal, additional

Published
2021
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41. The Genomic Landscape of Waldenström Macroglobulinemia Reveals Sustained Germinal Center Activity and Late-Developing Copy Number Aberrations

Author

Maclachlan, Kylee H, primary, Bagratuni, Tina, additional, Kastritis, Efstathios, additional, Ziccheddu, Bachisio, additional, Lu, Sydney X., additional, Yellapantula, Venkata D, additional, Famulare, Christopher, additional, Diamond, Benjamin, additional, Chojnacka, Monika, additional, Raj, Arjun, additional, Mason, Emilia, additional, Coffey, David G., additional, Hoffman, James E., additional, Kazandjian, Dickran, additional, Derkach, Andriy, additional, Papaemmanuil, Elli, additional, Dogan, Ahmet, additional, Lesokhin, Alexander, additional, Landgren, Ola, additional, Palomba, M. Lia, additional, Maura, Francesco, additional, and Dimopoulos, Meletios-Athanasios, additional

Published
2021
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42. Safety and Efficacy of CPX-351 in Younger Patients < 60 Years Old with Secondary Acute Myeloid Leukemia: An Updated Analysis

Author

Przespolewski, Amanda, primary, Goldberg, Aaron D, additional, Talati, Chetasi, additional, Fazal, Salman, additional, Vachhani, Pankit, additional, Sanikommu, Srinivasa Reddy R., additional, Thota, Swapna, additional, Waksal, Julian, additional, Ball, Brian, additional, Famulare, Christopher, additional, Stahl, Maximilian, additional, Mckinnell, Zoe, additional, Baron, Jeffrey, additional, Griffiths, Elizabeth A., additional, Thompson, James E., additional, Sweet, Kendra, additional, and Wang, Eunice S., additional

Published
2021
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43. Multicenter evaluation of efficacy and toxicity of venetoclax‐based combinations in patients with accelerated and blast phase myeloproliferative neoplasms

Author

King, Amber C., primary, Weis, Taylor M., additional, Derkach, Andriy, additional, Ball, Somedeb, additional, Pandey, Manu, additional, Mauro, Michael J., additional, Goldberg, Aaron D., additional, Stahl, Maximilian, additional, Famulare, Christopher, additional, Tallman, Martin S., additional, Wang, Eunice S., additional, Kuykendall, Andrew T., additional, and Rampal, Raajit K., additional

Published
2021
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44. Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant

Author

Bewersdorf, Jan Philipp, primary, Derkach, Andriy, additional, Gowda, Lohith, additional, Menghrajani, Kamal, additional, DeWolf, Susan, additional, Ruiz, Josel D., additional, Ponce, Doris M., additional, Shaffer, Brian C., additional, Tamari, Roni, additional, Young, James W., additional, Jakubowski, Ann A., additional, Gyurkocza, Boglarka, additional, Chan, Alexander, additional, Xiao, Wenbin, additional, Glass, Jacob, additional, King, Amber C., additional, Cai, Sheng F., additional, Daniyan, Anthony, additional, Famulare, Christopher, additional, Cuello, Bernadette M., additional, Podoltsev, Nikolai A., additional, Roshal, Mikhail, additional, Giralt, Sergio, additional, Perales, Miguel-Angel, additional, Seropian, Stuart, additional, Cho, Christina, additional, Zeidan, Amer M., additional, Prebet, Thomas, additional, Stein, Eytan M., additional, Tallman, Martin S., additional, Goldberg, Aaron D., additional, and Stahl, Maximilian, additional

Published
2021
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45. Clinical Factors but Not Somatic Mutations Predict for Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplant: Analysis of the North American Myelofibrosis Transplant Outcome (NAMTO) Study

Author

Ajufo, Helen, Derkach, Andriy, Rampal, Raajit K., Famulare, Christopher, Nemirovsky, David, Chervin, Jordan, Ho, Vincent, Gupta, Vikas, Viswabandya, Auro, Deeg, H. Joachim, Monahan, Tim, Jain, Tania, Jones, Richard J., Palmer, Jeanne, Gerds, Aaron T., Keyzner, Alla, Lagdameo, Jonathan, Gomez-Arteaga, Alexandra, Van Besien, Koen, Podoltsev, Nikolai A., Puzo, Christian, Kosuri, Satyajit, Amanam, Idoroenyi, and Tamari, Roni

Published
2023
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46. Deconvoluting Clonal and Cellular Architecture in IDH-Mutant Acute Myeloid Leukemia

Author

Sirenko, Maria, Lee, Soobeom, Sun, Zhengxi, Chaligne, Ronan, Asimomitis, Georgios, Brierley, Charlotte K, Bernard, Elsa, Cai, Sheng F., Myers, Robert M, Nadorp, Bettina, Levine, Max F, Domenico, Dylan, Arango Ossa, Juan E, Medina Martinez, Juan Santiago, Menghrajani, Kamal, Lasry, Audrey, Mims, Alice, Desai, Helee, Laganson, Andrea, Famulare, Christopher, Patel, Minal, Lozanski, Gerard, Loghavi, Sanam, Bolton, Kelly L., Viny, Aaron D., Roshal, Mikhail, Levine, Ross L, Stein, Eytan M., Landau, Dan A., Eisfeld, Ann-Kathrin, Aifantis, Iannis, and Papaemmanuil, Elli

Published
2023
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