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Articles 31 - 43 of 43
Full-Text Articles in Hematology
Follicular Lymphoma Microenvironment Characteristics Associated With Tumor Cell Mutations And Mhc Class Ii Expression, Guangchun Han, Qing Deng, Mario L Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J Nomie, Alexander Bagaev, Edwin R Parra, Luisa M Solis Soto, Simrit Parmar, Fredrick B Hagemeister, Sairah Ahmed, Swaminathan P Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H Fowler, Christopher R Flowers, Paolo Strati, Jason R Westin, Sattva S Neelapu, Loretta J Nastoupil, Francisco Vega, Linghua Wang, Michael R Green
Follicular Lymphoma Microenvironment Characteristics Associated With Tumor Cell Mutations And Mhc Class Ii Expression, Guangchun Han, Qing Deng, Mario L Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J Nomie, Alexander Bagaev, Edwin R Parra, Luisa M Solis Soto, Simrit Parmar, Fredrick B Hagemeister, Sairah Ahmed, Swaminathan P Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H Fowler, Christopher R Flowers, Paolo Strati, Jason R Westin, Sattva S Neelapu, Loretta J Nastoupil, Francisco Vega, Linghua Wang, Michael R Green
Faculty, Staff and Student Publications
Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with …
Pure Erythroid Leukemia Is Characterized By Biallelic Tp53 Inactivation And Abnormal P53 Expression Patterns In De Novo And Secondary Cases, Hong Fang, Sa A Wang, Joseph D Khoury, Siba El Hussein, Do Hwan Kim, Mehrnoosh Tashakori, Zhenya Tang, Shaoying Li, Zhihong Hu, Fatima Zahra Jelloul, Keyur P Patel, Timothy J Mcdonnell, Tapan Kadia, L Jeffrey Medeiros, Wei Wang
Pure Erythroid Leukemia Is Characterized By Biallelic Tp53 Inactivation And Abnormal P53 Expression Patterns In De Novo And Secondary Cases, Hong Fang, Sa A Wang, Joseph D Khoury, Siba El Hussein, Do Hwan Kim, Mehrnoosh Tashakori, Zhenya Tang, Shaoying Li, Zhihong Hu, Fatima Zahra Jelloul, Keyur P Patel, Timothy J Mcdonnell, Tapan Kadia, L Jeffrey Medeiros, Wei Wang
Faculty, Staff and Student Publications
No abstract provided.
Immunophenotypic And Molecular Features Of Acute Myeloid Leukemia With Plasmacytoid Dendritic Cell Differentiation Are Distinct From Blastic Plasmacytoid Dendritic Cell Neoplasm, Wei Wang, Jie Xu, Joseph D Khoury, Naveen Pemmaraju, Hong Fang, Roberto N Miranda, C Cameron Yin, Siba El Hussein, Fuli Jia, Zhenya Tang, Shimin Hu, Marina Konopleva, L Jeffrey Medeiros, Sa A Wang
Immunophenotypic And Molecular Features Of Acute Myeloid Leukemia With Plasmacytoid Dendritic Cell Differentiation Are Distinct From Blastic Plasmacytoid Dendritic Cell Neoplasm, Wei Wang, Jie Xu, Joseph D Khoury, Naveen Pemmaraju, Hong Fang, Roberto N Miranda, C Cameron Yin, Siba El Hussein, Fuli Jia, Zhenya Tang, Shimin Hu, Marina Konopleva, L Jeffrey Medeiros, Sa A Wang
Faculty, Staff and Student Publications
Acute myeloid leukemia (AML) with ≥2% plasmacytoid dendritic cells (pDC) has been recently described as AML with pDC differentiation (pDC-AML) characterized by pDC expansion with frequent RUNX1 mutations. In this study, we investigated a cohort of 53 pDC-AML cases representing about 3% of all AML cases. We characterized their immunophenotype and genetic profiles and compared these findings with blastic plasmacytoid dendritic cell neoplasm (BPDCN). pDC-differentiation/expansion was preferentially observed in AML with an immature myeloid or myelomonocytic immunophenotype, where myeloblasts were frequently positive for CD34 (98%), CD117 (94%), HLA-DR (100%) and TdT (79%), with increased CD123 (89%) expression. The median number …
Tp53 Copy Number And Protein Expression Inform Mutation Status Across Risk Categories In Acute Myeloid Leukemia, Mehrnoosh Tashakori, Tapan Kadia, Sanam Loghavi, Naval Daver, Rashmi Kanagal-Shamanna, Sherry Pierce, Dawen Sui, Peng Wei, Farnoosh Khodakarami, Zhenya Tang, Mark Routbort, Carol A Bivins, Elias J Jabbour, L Jeffrey Medeiros, Kapil Bhalla, Hagop M Kantarjian, Farhad Ravandi, Joseph D Khoury
Tp53 Copy Number And Protein Expression Inform Mutation Status Across Risk Categories In Acute Myeloid Leukemia, Mehrnoosh Tashakori, Tapan Kadia, Sanam Loghavi, Naval Daver, Rashmi Kanagal-Shamanna, Sherry Pierce, Dawen Sui, Peng Wei, Farnoosh Khodakarami, Zhenya Tang, Mark Routbort, Carol A Bivins, Elias J Jabbour, L Jeffrey Medeiros, Kapil Bhalla, Hagop M Kantarjian, Farhad Ravandi, Joseph D Khoury
Faculty, Staff and Student Publications
Mutant TP53 is an adverse risk factor in acute myeloid leukemia (AML), but large-scale integrated genomic-proteomic analyses of TP53 alterations in patients with AML remain limited. We analyzed TP53 mutational status, copy number (CN), and protein expression data in AML (N = 528) and provide a compilation of mutation sites and types across disease subgroups among treated and untreated patients. Our analysis shows differential hotspots in subsets of AML and uncovers novel pathogenic variants involving TP53 splice sites. In addition, we identified TP53 CN loss in 70.2% of TP53-mutated AML cases, which have more deleterious TP53 mutations, as well as …
Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nicholas Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian
Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nicholas Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian
Faculty, Staff and Student Publications
Progress with intensive chemotherapy and supportive care measures has improved survival in newly diagnosed acute myeloid leukemia (AML). Predicting outcome helps in treatment decision making. We analyzed survival as the treatment endpoint in 3728 patients with newly diagnosed AML treated with intensive chemotherapy from 1980 to 2021. We divided the total study group (3:1 basis) into a training (n = 2790) and a validation group (n = 938). The associations between survival and 27 characteristics were investigated. In the training cohort, the multivariate analysis identified 12 consistent adverse prognostic variables independently associated with worse survival: older age, therapy-related myeloid neoplasm, …
Resistance To Targeted Therapies: Delving Into Flt3 And Idh, Sai Prasad Desikan, Naval Daver, Courtney Dinardo, Tapan Kadia, Marina Konopleva, Farhad Ravandi
Resistance To Targeted Therapies: Delving Into Flt3 And Idh, Sai Prasad Desikan, Naval Daver, Courtney Dinardo, Tapan Kadia, Marina Konopleva, Farhad Ravandi
Faculty, Staff and Student Publications
Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.
Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Burcu Aslan, Gorkem Kismali, Lakesla R Iles, Ganiraju C Manyam, Mary L Ayres, Lisa S Chen, Mihai Gagea, Maria Teresa Sabrina Bertilaccio, William G Wierda, Varsha Gandhi
Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Burcu Aslan, Gorkem Kismali, Lakesla R Iles, Ganiraju C Manyam, Mary L Ayres, Lisa S Chen, Mihai Gagea, Maria Teresa Sabrina Bertilaccio, William G Wierda, Varsha Gandhi
Faculty, Staff and Student Publications
Pirtobrutinib (LOXO-305), a reversible inhibitor of Bruton's tyrosine kinase (BTK), was designed as an alternative strategy to treat ibrutinib-resistant disease that develops due to C481 kinase domain mutations. The clinical activity of pirtobrutinib has been demonstrated in CLL, but the mechanism of action has not been investigated. We evaluated pirtobrutinib in 4 model systems: first, MEC-1, a CLL cell line overexpressing BTKWT, BTKC481S, or BTKC481R; second, murine models driven by MEC-1 overexpressing BTKWT or BTKC481S; third, in vitro incubations of primary CLL cells; and finally, CLL patients during pirtobrutinib therapy (NCT03740529, ClinicalTrials.gov). Pirtobrutinib inhibited BTK activation as well …
Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel
Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel
Faculty, Staff and Student Publications
NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3' UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture …
Proteomic Profiling Based Classification Of Cll Provides Prognostication For Modern Therapy And Identifies Novel Therapeutic Targets, Ti'ara L Griffen, Fieke W Hoff, Yihua Qiu, James W Lillard, Alessandra Ferrajoli, Philip Thompson, Endurance Toro, Kevin Ruiz, Jan Burger, William Wierda, Steven M Kornblau
Proteomic Profiling Based Classification Of Cll Provides Prognostication For Modern Therapy And Identifies Novel Therapeutic Targets, Ti'ara L Griffen, Fieke W Hoff, Yihua Qiu, James W Lillard, Alessandra Ferrajoli, Philip Thompson, Endurance Toro, Kevin Ruiz, Jan Burger, William Wierda, Steven M Kornblau
Faculty, Staff and Student Publications
Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered. SG membership superseded other prognostic factors (Rai Staging, …
Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M Vose, Matthew A Lunning, Aliyah R Sohani, Benjamin J Chen, Shannon Buckley, Loretta J Nastoupil, R Eric Davis, Jason R Westin, Nathan H Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J Rodig, Adnan Mansoor, Michael R Green
Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M Vose, Matthew A Lunning, Aliyah R Sohani, Benjamin J Chen, Shannon Buckley, Loretta J Nastoupil, R Eric Davis, Jason R Westin, Nathan H Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J Rodig, Adnan Mansoor, Michael R Green
Faculty, Staff and Student Publications
B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, …
Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla
Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla
Faculty, Staff and Student Publications
The majority of RUNX1 mutations in acute myeloid leukemia (AML) are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared with AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1, and c-Myc. Compared with AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. Homoharringtonine treatment repressed …
Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel
Targeted Mutational Profiling Of Peripheral T-Cell Lymphoma Not Otherwise Specified Highlights New Mechanisms In A Heterogeneous Pathogenesis., J. H. Schatz, S. M. Horwitz, J. Teruya-Feldstein, Matthew A. Lunning, A. Viale, K. Huberman, N. D. Socci, N. Lailler, A. Heguy, I. Dolgalev, J. C. Migliacci, M. Pirun, M. L. Palomba, D. M. Weinstock, H-G Wendel
Journal Articles: Oncology and Hematology
No abstract provided.
Glanzmann Thrombasthenia. Cooperation Between Sequence Variants In Cis During Splice Site Selection., Ying Jin, Harry C. Dietz, Robert A. Montgomery, William R. Bell, Iain Mcintosh, Barry Coller, Paul F. Bray
Glanzmann Thrombasthenia. Cooperation Between Sequence Variants In Cis During Splice Site Selection., Ying Jin, Harry C. Dietz, Robert A. Montgomery, William R. Bell, Iain Mcintosh, Barry Coller, Paul F. Bray
Cardeza Foundation for Hematologic Research
Glanzmann thrombasthenia (GT), an autosomal recessive bleeding disorder, results from abnormalities in the platelet fibrinogen receptor, GP(IIb)-IIIa (integrin alpha(IIb)beta3). A patient with GT was identified as homozygous for a G-->A mutation 6 bp upstream of the GP(IIIa) exon 9 splice donor site. Patient platelet GP(IIIa) transcripts lacked exon 9 despite normal DNA sequence in all of the cis-acting sequences known to regulate splice site selection. In vitro analysis of transcripts generated from mini-gene constructs demonstrated that exon skipping occurred only when the G-->A mutation was cis to a polymorphism 116 bp upstream, providing precedence that two sequence variations …