Article
Oncology
Ka-Yuk Yuen, Yong Liu, Yong-Zhuo Zhou, Yin Wang, Dun-Hua Zhou, Jian-Pei Fang, Lu-Hong Xu
Summary: This study analyzed the mutational landscape of 11q23/KMT2A-rearranged pediatric AML and assessed their prognostic value in outcomes. The results showed that pediatric AML patients with 11q23/KMT2A-rearrangements had a low number of mutations, with most involving RAS pathway mutations. Compared to non-11q23/KMT2A-rearranged AML, 11q23/KMT2A-rearranged AML had significantly higher incidence of KRAS and SETD2 gene mutations. KRAS mutations were associated with worse 5-year event-free survival and overall survival, while SETD2 mutations increased the 5-year relapse rate.
Review
Oncology
Hanadi El Achi, Rashmi Kanagal-Shamanna
Summary: NGS is routinely used for mutation profiling in acute myeloid leukemia, with results driving AML phenotype and guiding targeted therapies. Molecular findings have been incorporated into WHO sub-classifications and integrated into treatment guidelines by the European Leukemia Net. NGS mutation profiling provides essential information for diagnosis and treatment in AML, and offers valuable insights into disease ontogeny, resistance monitoring, and other aspects beyond routine clinical applications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Harrison K. Tsai, Christopher J. Gibson, H. Moses Murdock, Phani Davineni, Marian H. Harris, Eunice S. Wang, Lukasz P. Gondek, Annette S. Kim, Valentina Nardi, R. Coleman Lindsley
Summary: The study reveals the presence of complex secondary events in patients with KMT2A-PTD, which may be related to the occurrence and relapse of acute myeloid leukemia and myelodysplastic syndrome.
Article
Medicine, General & Internal
Fang Chen, Ying Yang, Shuang Fu
Summary: KMT2A-SEPT6 fusion gene is relatively rare in leukemia and its clinical features and prognosis are still unclear. This study found that KMT2A-SEPT6 is more commonly observed in pediatric AML patients, some of whom may have NRAS gene mutations. The prognosis is related to white blood cell levels and leukemia subtype, but not related to age or bone marrow transplantation.
FRONTIERS IN MEDICINE
(2022)
Review
Oncology
Lamia Madaci, Laure Farnault, Norman Abbou, Jean Gabert, Geoffroy Venton, Regis Costello
Summary: Cytological approaches have been used for the diagnosis, prognosis, and management of acute myeloid leukemia (AML) and myelodysplastic neoplasms. Technological advances in molecular biology, particularly next-generation sequencing (NGS), have made it possible to quickly identify gene mutations in AML and MDS. The combination of cytological approaches and NGS enables better clinical management and improved prognosis for patients with acute leukemia and myelodysplastic neoplasms.
Article
Oncology
Mengzhen Wang, Ruiqi Wang, Hong Wang, Chongjian Chen, Jiayue Qin, Xiaoning Gao, Li Yu
Summary: This study analyzed the genetic mutation profile of previously untreated acute myeloid leukemia (AML) patients and compared the gene mutation spectrum of refractory/relapsed (R/R) AML patients to newly diagnosed ones. The findings show increased frequencies of tumor suppressor mutations in relapsed AML, and decreased mutation frequencies in specific genes. FLT3-ITD mutation predicted poorer outcomes in terms of complete remission and overall survival in refractory AML and relapsed patients.
LEUKEMIA & LYMPHOMA
(2021)
Article
Oncology
Jong-Mi Lee, Silvia Park, Insik Hwang, Dain Kang, Byung Sik Cho, Hee-Je Kim, Ari Ahn, Myungshin Kim, Yonggoo Kim
Summary: This article presents an ITD-tracing algorithm based on NGS method for monitoring MRD in AML patients. The assay shows high sensitivity and superior performance, and demonstrates prognostic value in AML patients undergoing allogeneic hematopoietic stem cell transplantation.
Article
Oncology
Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. Wong, Charlie Hatton, Christian Marinaccio, Florian Perner, Masooma Rajput, Noa J. C. Antonissen, Yanhe Wen, Lu Yang, Lorenzo Brunetti, Chun -Wei Chen, Scott A. Armstrong
Summary: The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Most patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1, with an NPM1 mutation (NPM1c) being common in these cases. This study reveals that NPM1c directly binds to specific chromatin targets, collaborates with the MLL1 complex, and directly regulates oncogenic gene expression in AML.
Article
Oncology
Biao Wang, Bin Yang, Wei Wu, Xuan Liu, Haiqian Li
Summary: This study investigated the correlation between genotypic profiles and clinicopathologic characteristics in AML patients with NPM1 mutation. The co-occurring mutations in signaling pathways and methylation modifiers were found to be associated with the expressions of specific markers, providing mechanistic insights into the immunophenotypic heterogeneity of AML with NPM1 mutation.
Article
Biology
Miaoran Xia, Lina Wu, Xiaoping Sun, Xin Han, Huige Yan, Jing Huang, Youhui Zhang, Zhihong Hu, Youli Zu, C. Cameron Yin, Xiaoyan Qiu
Summary: Identifying new molecular targets is crucial for prognosis prediction and target therapy of acute myeloid leukemia (AML). This study found that higher levels of immunoglobulin (Ig) expression in myeloblasts were associated with significantly shorter disease-free survival in AML patients. Next-generation sequencing revealed dysregulated Ig transcripts and biased V-H-D-J(H) rearrangements in AML. These findings suggest the potential of Ig expression and repertoire as novel markers for disease monitoring and target therapy in AML.
Article
Oncology
Sonia Matos, Paulo Bernardo, Susana Esteves, Aida Botelho de Sousa, Marcos Lemos, Patricia Ribeiro, Madalena Silva, Albertina Nunes, Joana Lobato, Maria de Jesus Frade, Maria Gomes da Silva, Sergio Chacim, Jose Mariz, Graca Esteves, Joao Raposo, Ana Espadana, Jose Carda, Pedro Barbosa, Vania Martins, Maria Carmo-Fonseca, Joana Desterro
Summary: This study aimed to evaluate the clinical value of screening a targeted gene panel by next-generation sequencing (NGS) in acute myeloid leukemia (AML) patients. The researchers prospectively analyzed 268 newly diagnosed AML patients and found that access to NGS data improved risk assessment for approximately 23% of the patients, leading to unexpected results associated with mutations in the FLT3 gene. The study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and emphasizes the need for further studies to refine the current risk classification criteria.
Article
Pathology
Krizsan Szilvia, Peterffy Borbala, Egyed Balint, Nagy Tibor, Sebestyen Endre, Leszlo Hegyi Lajos, Jakab Zsuzsanna, J. Erdelyi Deniel, Muller Judit, Peter Gyorgy, Csanedi Krisztina, Kellay Krisztian, Krivan Gergely, Barna Gabor, Bedics Gabor, Haltrich Iren, Ottoffy Gabor, Csernus Katalin, Vojcek Agnes, Gyoergyi Tiszlavicz Lilla, Mita Gebor Krisztina, Kelemen Agnes, Hauser Peter, Gaal Zsuzsanna, Szegedi Istvan, Ujfalusi Aniko, Kajtar Bela, Kiss Csongor, Matolcsy Andras, Timar Botond, Kovacs Gabor, Alpar Donat, Bodor Csaba
Summary: This study provides an integrative analysis of the molecular landscape of pediatric acute myeloid leukemia (AML). It reveals differences in the mutational profiles compared to previous studies, identifies novel recurrent mutations, and highlights the association of certain mutations with treatment resistance and disease progression. The findings contribute to improved molecular characterization and risk stratification of pediatric AML.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Article
Oncology
Huan-Ping Wang, Jun-Jun He, Qiao-Yun Zhu, Lin Wang, Jian-Hu Li, Jian-Song Huang, Wan-Zhuo Xie, Hong-Hu Zhu, Jie Jin
Summary: The NUP214-ABL1 fusion gene is commonly detected in T-ALL and B-ALL patients, but has not been reported in AML. The sensitivity of NUP214-ABL1-positive patients to TKIs remains controversial, and further case studies will provide insights into treatment and prognosis assessments.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Lina Marie Hoffmeister, Eser Orhan, Christiane Walter, Naghmeh Niktoreh, Helmut Hanenberg, Nils von Neuhoff, Dirk Reinhardt, Markus Schneider
Summary: KMT2A rearrangements are common in pediatric AML and are important for risk group stratification. This study analyzed a cohort of 967 pediatric AML patients, finding no impact of KMT2A-r on overall survival when subgroups were combined, but showing different prognosis in various subgroups. KMT2A-r is correlated with KRAS mutations and has less FLT3-ITDs, while being mutually exclusive with other genetic mutations. Additionally, CSPG4 expression is correlated with KMT2A-r but does not have a significant prognostic impact.
Article
Genetics & Heredity
Sorina Mihaela Papuc, Alina Erbescu, Diana Cisleanu, Diana Ozunu, Cristina Enache, Ion Dumitru, Elena Lupoaia Andrus, Mihaela Gaman, Viola Maria Popov, Maria Dobre, Oana Stanca, Silvana Angelescu, Nicoleta Berbec, Andrei Colita, Ana-Maria Vladareanu, Horia Bumbea, Aurora Arghir
Summary: Integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance, providing insights for personalized treatment of AML patients.
Letter
Oncology
Alice S. Mims, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Krzysztof Mrozek, James S. Blachly, Shelley Orwick, Dimitrios Papaioannou, Deedra Nicolet, Deepa Sampath, Richard M. Stone, Bayard L. Powell, Jonathan E. Kolitz, John C. Byrd, Clara D. Bloomfield
Article
Biophysics
Madlen Jentzsch, Juliane Grimm, Marius Bill, Dominic Brauer, Donata Backhaus, Karoline Goldmann, Julia Schulz, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind
Summary: Secondary or therapy-related acute myeloid leukemia (s/tAML) patients have inferior outcomes after chemotherapy and often receive allogeneic stem cell transplantation for consolidation. In the ELN favorable risk group, s/tAML patients have a higher cumulative incidence of relapse compared to de novo AML patients. However, outcomes are similar between de novo and s/tAML patients in the ELN intermediate and adverse risk group.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Tanja Holzhey, Wolfram Poenisch, Song-Yau Wang, Madlen Holzvogt, Bruno Holzvogt, Marc Andrea, Thomas Zehrfeld, Doreen Hammerschmidt, Franz Albert Hoffmann, Cornelia Becker, Andreas Schwarzer, Maik Schwarz, Uta Schoenfelder-Fricke, Thomas Edelmann, Leanthe Braunert, Georg-Nikolaus Franke, Madlen Jentzsch, Sebastian Schwind, Markus Bill, Juliane Grimm, Yvonne Remane, Uwe Platzbecker, Markus Scholz
Summary: The study results suggest that a rapid decrease in iFLC on day 8 is an early prognostic marker for newly diagnosed MM patients undergoing BPV treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Oncology
Pu Zhang, Lindsey T. Brinton, Katie Williams, Steven Sher, Shelley Orwick, Lai Tzung-Huei, Alice S. Mims, Christopher C. Coss, Samuel K. Kulp, Youssef Youssef, Wing Keung Chan, Shaneice Mitchell, Allison Mustonen, Matthew Cannon, Hannah Phillips, Amy M. Lehman, Tierney Kauffman, Larry Beaver, Daniel Canfield, Nicole R. Grieselhuber, Lapo Alinari, Deepa Sampath, Pearlly Yan, John C. Byrd, James S. Blachly, Rosa Lapalombella
Summary: The study identified two histone deacetylases, HDAC8 and SIRT6, whose knockout conferred synthetic lethality with the NAMPT inhibitor KPT-9274 in AML. Combination therapy with HDAC8-specific inhibitor or class I HDAC inhibitor synergistically decreased AML cell survival in a dose-dependent manner, with promising in vivo efficacy compared to monotherapy. Genetic inhibition of SIRT6 potentiated the effect of KPT-9274 on DNA repair deficiencies, suggesting a rationale for a novel combination-based treatment for AML.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Christopher J. Walker, Krzysztof Mrozek, Hatice Gulcin Ozer, Deedra Nicolet, Jessica Kohlschmidt, Dimitrios Papaioannou, Luke K. Genutis, Marius Bill, Bayard L. Powell, Geoffrey L. Uy, Jonathan E. Kolitz, Andrew J. Carroll, Richard M. Stone, Ramiro Garzon, John C. Byrd, Ann-Kathrin Eisfeld, Albert de la Chapelle, Clara D. Bloomfield
Summary: This study identified a 10-gene signature predictive of relapse in adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) through RNA sequencing, showing strong predictive value and potential clinical application in prognostic stratification.
Article
Hematology
Sydney Fobare, Jessica Kohlschmidt, Hatice Gulcin Ozer, Krzysztof Mrozek, Deedra Nicolet, Alice S. Mims, Ramiro Garzon, James S. Blachly, Shelley Orwick, Andrew J. Carroll, Richard M. Stone, Eunice S. Wang, Jonathan E. Kolitz, Bayard L. Powell, Christopher C. Oakes, Ann-Kathrin Eisfeld, Erin Hertlein, John C. Byrd
Summary: This study investigated the prognostic factors associated with chemotherapy outcomes in patients with acute myeloid leukemia (AML). The researchers found that mutations in the protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene co-occurred with other gene mutations and had different impacts on patient outcomes depending on the location of the PTPN11 mutation. Moreover, the presence of PTPN11 mutations in AML patients with wild-type NPM1 was associated with adverse outcomes.
Article
Hematology
Marius Bill, Madlen Jentzsch, Lara Bischof, Jessica Kohlschmidt, Juliane Grimm, Laura Katharina Schmalbrock, Donata Backhaus, Dominic Brauer, Karoline Goldmann, Georg -Nikolaus Franke, Vladan Vucinic, Dietger Niederwieser, Alice S. Mims, Uwe Platzbecker, Ann-Kathrin Eisfeld, Sebastian Schwind
Summary: Somatic mutations in IDH1 and IDH2 genes are common in AML. The presence of IDH mutations may not significantly impact the prognosis of AML patients consolidated by HSCT, but specific mutation locations (IDH1 R132, IDH2 R140, and IDH2 R172) and mutation dynamics do affect the risk of relapse. IDH2 R140 mutations behave more like clonal hematopoiesis-related aberrations, while IDH1 R132 and IDH2 R172 harbor AML disease-specific features.
Article
Oncology
Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J. Johnson, Melanie M. Frigault, Joy M. Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C. Byrd, Rosa Lapalombella
Summary: The highly selective inhibitor VIP152 of CDK9 has shown promising results in treating chronic lymphocytic leukemia (CLL), reducing disease burden and improving overall survival rates.
Article
Oncology
Eric D. D. Eisenmann, Jack C. C. Stromatt, Sydney Fobare, Kevin M. M. Huang, Daelynn R. R. Buelow, Shelley Orwick, Jae Yoon Jeon, Robert H. H. Weber, Bill Larsen, Alice S. S. Mims, Erin Hertlein, John C. C. Byrd, Sharyn D. D. Baker
Summary: This study investigates the preclinical activity of TP-0903, a multikinase inhibitor, in TP53 mutant AML. It demonstrates that TP-0903 inhibits cell viability and induces apoptosis in TP53 mutant AML cells, and combination with decitabine improves survival in xenograft models. These findings support the clinical evaluation of TP-0903 in combination with decitabine in TP53 mutant AML.
Article
Oncology
Krzysztof Mrozek, Jessica Kohlschmidt, James S. Blachly, Deedra Nicolet, Andrew J. Carroll, Kellie J. Archer, Alice S. Mims, Karilyn T. Larkin, Shelley Orwick, Christopher C. Oakes, Jonathan E. Kolitz, Bayard L. Powell, William G. Blum, Guido Marcucci, Maria R. Baer, Geoffrey L. Uy, Wendy Stock, John C. Byrd, Ann-Kathrin Eisfeld
Summary: Recently, the European LeukemiaNet revised the genetic-risk classification of acute myeloid leukemia (AML), leading to changes in the percentage of patients in different risk groups. The new classification accurately reflected treatment outcomes in most patients, but there were discrepancies in certain age and ethnic groups. The prediction abilities of the new and old classifications were similar, and the significance of some newly added markers was confirmed and challenged.
Letter
Hematology
Bhavana Bhatnagar, Jessica Kohlschmidt, Shelley J. Orwick, Daelynn R. Buelow, Sydney Fobare, Christopher C. Oakes, Jonathan E. Kolitz, Geoff Uy, Wendy Stock, Bayard L. Powell, Deedra Nicolet, Erin K. Hertlein, Krzysztof Mrozek, James S. Blachly, Ann-Kathrin Eisfeld, Sharyn D. Baker, John C. Byrd
Letter
Hematology
Melanie Rebechi, Jessica Kohlschmidt, Krzysztof Mrozek, Deedra Nicolet, Alice S. Mims, James S. Blachly, Shelley Orwick, Karilyn T. Larkin, Christopher C. Oakes, Andrew Hantel, Andrew J. Carroll, William G. Blum, Bayard L. Powell, Geoffrey L. Uy, Richard M. Stone, Richard A. Larson, John C. Byrd, Electra D. Paskett, Jesse J. Plascak, Ann-Kathrin Eisfeld
Article
Hematology
Dimitrios Papaioannou, Hatice G. Ozer, Deedra Nicolet, Amog P. Urs, Tobias Herold, Krzysztof Mrozek, Aarif M. N. Batcha, Klaus H. Metzeler, Ayse S. Yilmaz, Stefano Volinia, Marius Bill, Jessica Kohlschmidt, Maciej Pietrzak, Christopher J. Walker, Andrew J. Carroll, Jan Braess, Bayard L. Powell, Ann-Kathrin Eisfeld, Geoffrey L. Uy, Eunice S. Wang, Jonathan E. Kolitz, Richard M. Stone, Wolfgang Hiddemann, John C. Byrd, Clara D. Bloomfield, Ramiro Garzon
Summary: The expression levels of long non-coding RNA (lncRNA) have been found to be associated with the clinical outcome of cytogenetically normal acute myeloid leukemia (CN-AML) patients. However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients remain unknown. In this study, we analyzed RNA sequencing data of 377 younger adults with CN-AML and identified recurrent genetic variants in lncRNA that are expressed in leukemic blasts. We found that the cytosine-to-thymidine variants in the lncRNA RP5-1074L1.4 and SNHG15 were independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant also correlated with better outcome in an independent dataset of CN-AML patients. Furthermore, overexpression of the wild-type SNHG15 lncRNA was associated with higher proliferation rate of leukemic blasts compared to the cytosine-to-thymidine variant.
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.
