Article
Oncology
Young Hoon Park, Sewon Lee, Yeung-Chul Mun, Dong Jin Park
Summary: This study compared the impact of ELN and mELN criteria on the development of HU resistance or intolerance in high-risk ET patients receiving HU treatment. The mELN criteria were found to more accurately identify HU resistance and intolerance and had an independent prognostic impact on transformation-free survival. The mELN criteria can be used to identify high-risk ET patients who may benefit from second-line therapy.
Review
Oncology
Indu Raman, Sant-Rayn Pasricha, H. Miles Prince, Costas Yannakou
Summary: Polycythemia vera is a myeloproliferative neoplasm characterized by erythrocytosis and thrombosis, with aspirin, venesection, or cytoreductive therapy being the main management strategies. Hydroxyurea is the first-line cytoreductive therapy for high-risk patients, but it can be associated with toxicities and resistance. Other treatment options, such as interferon and ruxolitinib, are being evaluated for hydroxyurea resistant or intolerant patients with Polycythemia vera.
LEUKEMIA & LYMPHOMA
(2021)
Article
Hematology
Kittitat Chiaranairungrot, Komkrich Kaewpreechawat, Chanwit Sajai, Narueporn Pagowong, Nissa Sukarat, Pokpong Piriyakhuntorn, Thanawat Rattanathammethee, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Adisak Tantiworawit, Lalita Norasetthada, Ekarat Rattarittamrong
Summary: This study investigated the prevalence, clinical outcomes, and factors associated with hydroxyurea resistance or intolerance among patients with polycythemia vera and essential thrombocythemia. The study found that patients who had hydroxyurea resistance or intolerance had a significantly increased risk of bleeding events. Low baseline hemoglobin levels, age over 60, and splenomegaly were identified as risk factors for hydroxyurea resistance or intolerance.
Article
Oncology
Francesca Palandri, Elena Rossi, Giuseppe Auteri, Massimo Breccia, Simona Paglia, Giulia Benevolo, Elena M. Elli, Francesco Cavazzini, Gianni Binotto, Alessia Tieghi, Mario Tiribelli, Florian H. Heidel, Massimiliano Bonifacio, Novella Pugliese, Giovanni Caocci, Monica Crugnola, Francesco Mendicino, Alessandra D'Addio, Simona Tomassetti, Bruno Martino, Nicola Polverelli, Sara Ceglie, Camilla Mazzoni, Rikard Mullai, Alessia Ripamonti, Bruno Garibaldi, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Giuseppe A. Palumbo, Alessandro Andriani, Michele Cavo, Roberto Latagliata, Valerio De Stefano
Summary: The prognostic relevance of complete response to hydroxyurea, predictors of response, and patients' triggers for switching to ruxolitinib in polycythemia vera are uncertain. Many PV patients receive underdosed hydroxyurea, leading to lower response and toxicity rates. Splenomegaly and other symptoms are the main drivers for early switch to ruxolitinib despite poor response to hydroxyurea.
Article
Biochemistry & Molecular Biology
Ralfs Buks, Megane Brusson, Sylvie Cochet, Tatiana Galochkina, Bruno Cassinat, Ivan Nemazanyy, Thierry Peyrard, Jean-Jacques Kiladjian, Alexandre G. de Brevern, Slim Azouzi, Wassim El Nemer
Summary: MPNs are characterized by abnormal clonal expansion of hematopoietic stem cells, leading to a high risk of thrombosis and progression to myelofibrosis and leukemia. ABCG2 may play a role in multidrug resistance in MPNs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Douglas Tremblay, Lukas Ronner, Nikolai Podoltsev, Jason Gotlib, Mark Heaney, Andrew Kuykendall, Casey O'Connell, Jamile M. Shammo, Angela Fleischman, Ruben Mesa, Abdulraheem Yacoub, Ronald Hoffman, Erin Moshier, Nicole Zubizarreta, John Mascarenhas
Summary: The study found that discontinuation of ruxolitinib in polycythemia vera patients did not lead to adverse outcomes and was generally associated with favorable prognosis. However, the lack of available salvage therapies highlights the need for further therapeutic development in PV.
Article
Medicine, General & Internal
Emine Gulturk, Deniz Yilmaz, Gulru Birce Sonmezoz, Ezgi Simge Yildirim
Summary: This study compared the biochemical and clinical features of PV patients diagnosed using the 2016 WHO criteria with those missed by the 2008 criteria, and evaluated the impact of lowered thresholds on PV diagnosis. The number of PV diagnoses significantly increased with the introduction of the 2016 criteria, with higher red blood cell and lactate dehydrogenase values and lower lymphocyte counts in the newly diagnosed patients. These findings provide support for the diagnostic value of the 2016 WHO criteria and the lowered thresholds.
Article
Biochemistry & Molecular Biology
Srdan Verstovsek, Ivan Krecak, Florian H. Heidel, Valerio De Stefano, Kenneth Bryan, Mike W. Zuurman, Michael Zaiac, Mara Morelli, Aoife Smyth, Santiago Redondo, Erwan Bigan, Michael Ruhl, Christoph Meier, Magali Beffy, Jean-Jacques Kiladjian
Summary: The PV-AIM study used machine learning to identify markers of thromboembolic events (TE) in patients with polycythemia vera (PV). The study found that lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) are closely associated with TE risk, and can be used to identify high-risk patients.
Review
Hematology
Alberto Alvarez-Larran, Emanuela Sant'Antonio, Claire Harrison, Jean-Jacques Kiladjian, Martin Griesshammer, Ruben Mesa, Jean Christophe Ianotto, Francesca Palandri, Juan Carlos Hernandez-Boluda, Gunnar Birgegard, Jyoti Nangalia, Steffen Koschmieder, Elisa Rumi, Tiziano Barbui
Summary: The European LeukemiaNet identified unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and proposed 14 recommendations and 6 solution proposals. The experts highlighted potential areas of concern, including antiplatelet therapy, platelet count definition, treatment targets, and management in different patient populations. By consensus-based approaches, the network aimed to address uncertainties and improve patient care in this specific subset of myeloproliferative neoplasms.
LANCET HAEMATOLOGY
(2021)
Review
Oncology
Nabih Maslah, Lina Benajiba, Stephane Giraudier, Jean-Jacques Kiladjian, Bruno Cassinat
Summary: Myeloproliferative neoplasms are characterized by driver mutations targeting the JAK/STAT pathway and often display additional mutations targeting various pathways. The disease progression typically involves a chronic phase followed by an accelerated phase or transformation into more aggressive diseases. Recent studies have shed light on the rates and mechanisms of mutation acquisition and selection in hematopoietic cells, using novel techniques to decipher clonal architecture and mutation-induced cell modifications at the single cell level.
Article
Hematology
Nabih Maslah, Emmanuelle Verger, Stephane Giraudier, Mathias Chea, Ronald Hoffman, John Mascarenhas, Bruno Cassiant, Jean-Jacques Kiladjian
Summary: This study demonstrates the direct effect of MDM2 inhibition on the selection of MPN patients' cells harboring TP53 mutations. TP53 mutations are late events in MPN, mainly occurring in the driver clone, and clonal evolution frequently consists of sequential branching instead of linear consecutive acquisition of mutations in the same clone.
Review
Hematology
Monia Marchetti, Alessandro Maria Vannucchi, Martin Griesshammer, Claire Harrison, Steffen Koschmieder, Heinz Gisslinger, Alberto Alvarez-Larran, Valerio De Stefano, Paola Guglielmelli, Francesca Palandri, Francesco Passamonti, Giovanni Barosi, Richard T. Silver, Rudiger Hehlmann, Jean-Jacques Kiladjian, Tiziano Barbui
Summary: Polycythaemia vera is a disease that affects the quality of life, increases the risk of vascular events, and has the potential to progress. The treatment for this disease has been studied in several randomized trials, and new drugs such as ropeginterferon alfa-2b and ruxolitinib have been approved in Europe. The European LeukemiaNet (ELN) expert panel has provided recommendations for the use of these drugs in clinical practice.
LANCET HAEMATOLOGY
(2022)
Review
Medicine, General & Internal
Yajur Arya, Arshi Syal, Monica Gupta, Saurabh Gaba
Summary: Treatment modalities for polycythemia vera (PV) vary depending on the patient's risk level and symptoms, with options including interferons, hydroxyurea, and anagrelide. Prospective future treatments include a histone deacetylase inhibitor and a murine double minute 2 antagonist.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Stephania Contreras Castillo, Bertille Montibus, Azucena Rocha, Will Duke, Ferdinand von Meyenn, Donal McLornan, Claire Harrison, Ann Mullally, Reiner Schulz, Rebecca J. Oakey
Summary: Hydroxycarbamide (HC) is a cytoreductive drug used as a first-line treatment in myeloproliferative neoplasms, with emerging evidence suggesting a role in transcription modulation. Research has shown that HC affects gene expression and DNA methylation levels, impacting not only the cell cycle but also hematopoietic functions in murine hematopoietic stem cells. Additionally, HC has been found to restore abnormal methylation patterns in MPN patients, particularly at the SPI1 gene and its binding sites.
Article
Oncology
Jie Jin, Albert Qin, Lei Zhang, Weihong Shen, Wei Wang, Jingjing Zhang, Yaning Li, Daoxiang Wu, Zhijian Xiao
Summary: This study evaluates the safety, efficacy, and molecular response of ropeginterferon alpha-2b in Chinese patients with PV using the 250-350-500 mu g dosing schema. The results will be used to support the application for a biologics license for PV treatment in China.
Article
Oncology
Alberto Alvarez-Larran, Marta Garrote, Francisca Ferrer-Marin, Manuel Perez-Encinas, M. Isabel Mata-Vazquez, Beatriz Bellosillo, Eduardo Arellano-Rodrigo, Montse Gomez, Regina Garcia, Valentin Garcia-Gutierrez, Mercedes Gasior, Beatriz Cuevas, Anna Angona, Maria Teresa Gomez-Casares, Clara M. Martinez, Elena Magro, Rosa Ayala, Rafael del Orbe-Barreto, Raul Perez-Lopez, Maria Laura Fox, Jose-Maria Raya, Lucia Guerrero, Carmen Garcia-Hernandez, Gonzalo Caballero, Ilda Murillo, Blanca Xicoy, M. Jose Ramirez, Gonzalo Carreno-Tarragona, Juan Carlos Hernandez-Boluda, Arturo Pereira
Summary: The study suggests that ruxolitinib treatment may reduce the incidence of arterial thrombosis in PV patients resistant/intolerant to hydroxyurea, but did not demonstrate a disease-modifying effect of ruxolitinib in this population.
Article
Hematology
Valentin Garcia-Gutierrez, Juan Carlos Hernandez-Boluda
Summary: This review discusses the potential of a new BCR::ABL1 inhibitor, asciminib, in the treatment of chronic myeloid leukemia (CML) patients. The drug has the ability to overcome resistance/intolerance and has shown promising efficacy in CML patients who have failed at least two TKIs.
EXPERT REVIEW OF HEMATOLOGY
(2022)
Article
Oncology
Maria Garcia-Fortes, Juan C. Hernandez-Boluda, Alberto Alvarez-Larran, Jose M. Raya, Anna Angona, Natalia Estrada, Laura Fox, Beatriz Cuevas, Maria C. Garcia-Hernandez, Maria Teresa Gomez-Casares, Francisca Ferrer-Marin, Silvana Saavedra, Francisco Cervantes, Regina Garcia-Delgado
Summary: The presence of comorbidities in myelofibrosis patients can significantly impact survival outcomes, with conditions such as hypertension, smoking, dyslipidemia, and hepatitis C virus being the most adverse factors associated with reduced overall survival.
Letter
Hematology
Solano de la Asuncion Carlos, Estela Gimenez, Juan Carlos Hernandez-Boluda, Maria Jose Terol, Eliseo Albert, Javier Lopez-Jimenez, Valentin Garcia-Gutierrez, Rafael Andreu, Dolores Garcia, Maria Laura Fox, Maria Jose Remigia, Paula Amat, Carlos Solano, David Navarro
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Adrian Mosquera-Orgueira, Manuel Perez-Encinas, Alberto Hernandez-Sanchez, Teresa Gonzalez-Martinez, Eduardo Arellano-Rodrigo, Javier Martinez-Elicegui, Angela Villaverde-Ramiro, Jose-Maria Raya, Rosa Ayala, Francisca Ferrer-Marin, Maria-Laura Fox, Patricia Velez, Elvira Mora, Blanca Xicoy, Maria-Isabel Mata-Vazquez, Maria Garcia-Fortes, Anna Angona, Beatriz Cuevas, Maria-Alicia Senin, Angel Ramirez-Payer, Maria-Jose Ramirez, Raul Perez-Lopez, Sonia Gonzalez de Villambrosia, Clara Martinez-Valverde, Maria-Teresa Gomez-Casares, Carmen Garcia-Hernandez, Mercedes Gasior, Beatriz Bellosillo, Juan-Luis Steegmann, Alberto Alvarez-Larran, Jesus Maria Hernandez-Rivas, Juan Carlos Hernandez-Boluda
Summary: In this study, a prediction model called AIPSS-MF was developed based on 8 clinical variables at diagnosis, which accurately predicts overall survival and leukemia-free survival in patients with primary and secondary myelofibrosis.
Article
Hematology
Alejandro Berna-Erro, Girish Ramesh, Elena Delgado, Antonio J. Corbacho, Francisca Ferrer-Marin, Raul Teruel, Maria P. Granados, Juan A. Rosado, Pedro C. Redondo
Summary: This study investigated the changes in Ca2+ entry through the store-operated calcium entry (SOCE) mechanism in neonatal platelets. The results showed altered TG-evoked SOCE, different molecular weight forms of STIM1, and overexpression of SARAF in neonatal platelets compared to maternal and control women platelets. It was also found that CAPN1 may cleave STIM1 in neonatal platelets, impairing SARAF coupling after SOCE activation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rosa Cifuentes, Jose Padilla, Maria Eugenia de la Morena-Barrio, Belen de la Morena-Barrio, Carlos Bravo-Perez, Pedro Garrido-Rodriguez, Maria Llamas, Antonia Minano, Vicente Vicente, Maria Luisa Lozano, Javier Corral
Summary: Multiplex ligation-dependent probe amplification (MLPA) is effective in identifying genetic structural variants in SERPINC1 in 5% of antithrombin deficiency (ATD) cases. However, MLPA has limitations in detecting intronic structural variants, and can produce imprecise and false-positive results for genetic defects affecting MLPA probes. Validation of MLPA results is encouraged based on our study.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alvaro Diaz-Gonzalez, Elvira Mora, Gayane Avetisyan, Santiago Furio, Rosalia De la Puerta, Jose Vicente Gil, Alessandro Liquori, Eva Villamon, Carmen Garcia-Hernandez, Marta Santiago, Cristian Garcia-Ruiz, Marta Llop, Blanca Ferrer-Lores, Eva Barragan, Silvia Garcia-Palomares, Empar Mayordomo, Irene Luna, Ana Vicente, Lourdes Cordon, Leonor Senent, Alberto Alvarez-Larran, Jose Cervera, Javier De la Rubia, Juan Carlos Hernandez-Boluda, Esperanza Such
Summary: Cytogenetic assessment is crucial for myelofibrosis patients, but traditional techniques often fail to provide useful karyotypes. This study introduces optical genome mapping (OGM) as a promising method for high-resolution evaluation of chromosomal aberrations. OGM, combined with NGS, enabled risk classification in all cases, identifying additional cryptic aberrations and upgrading risk categories. The study highlights OGM as a valuable tool to improve disease risk stratification in myelofibrosis patients.
Article
Oncology
Lucia Perez-Lamas, Alejandro Luna, Concepcion Boque, Blanca Xicoy, Pilar Giraldo, Raul Perez Lopez, Concepcion Ruiz Nuno, Natalia de las Heras, Elvira Mora Castera, Javier Lopez Marin, Adrian Segura Diaz, Valle Gomez, Patricia Velez Tenza, Magdalena Sierra Pacho, Juan Antonio Vera Goni, Melania Moreno Vega, Alberto Alvarez-Larran, Montse Cortes, Manuel Perez Encinas, Patricia Carrascosa Mastell, Anna Angona, Ana Rosell, Sunil Lakhwani, Mercedes Colorado, Elena Ramila, Carlos Cervero, Beatriz Cuevas, Lucia Villalon Blanco, Raquel de Paz, Antonio Paz Coll, Maria Jose Fernandez, Luis Felipe Casado, Juan Manuel Alonso-Dominguez, Maria Magdalena Anguita Arance, Araceli Salamanca Cuenca, Antonio Jimenez-Velasco, Santiago Osorio Prendes, Marta Santaliestra, Maria Jose Lis Chulvi, Juan Carlos Hernandez-Boluda, Valentin Garcia-Gutierrez
Summary: After the introduction of asciminib as a treatment for chronic myeloid leukemia, there is still limited real-life data on its efficacy and toxicity profile. This study analyzed the toxicity profile of asciminib and its cross-toxicity risk with previous TKIs in patients with therapeutic failure. The results showed that asciminib has a good safety profile but may present a risk of cross-toxicity with classical TKIs for certain adverse effects.
Review
Oncology
Maria Luz Morales, Francisca Ferrer-Marin
Summary: This review discusses factors other than genetic alterations that may play a role in the origin, evolution, and progression of myeloproliferative neoplasms (MPNs). It highlights the importance of exploring non-genetic mechanisms and provides a summary of studies investigating these factors. These studies focus on MPN cell-intrinsic or -extrinsic factors and their interaction through various approaches.
Article
Hematology
Roni Tamari, Donal P. Mclornan, Kwang Woo Ahn, Noel Estrada-Merly, Juan Carlos Hernandez-Boluda, Sergio Giralt, Jeanne Palmer, Robert Peter Gale, Zachariah Defilipp, David I. Marks, Marjolein van der Poel, Leo F. Verdonck, Minoo Battiwalla, Miguel Angel Diaz, Vikas Gupta, Haris Ali, Mark Robert Litzow, Hillard M. Lazarus, Usama Gergis, Asad Bashey, Jane Liesveld, Shahrukh Hashmi, Jeffrey J. Pu, Amer Beitinjaneh, Christopher Bredeson, David Rizzieri, Bipin N. Savani, Muhammad Bilal Abid, Siddhartha Ganguly, Vaibhav Agrawal, Vera Ulrike Bacher, Baldeep Wirk, Tania Jain, Corey Cutler, Mahmoud Aljurf, Tamila Kindwall-Keller, Mohamed A. Kharfan-Dabaja, Gerhard C. Hildebrandt, Attaphol Pawarode, Melhem M. Solh, Jean A. Yared, Michael R. Grunwald, Sunita Nathan, Taiga Nishihori, Sachiko Seo, Bart L. Scott, Ryotaro Nakamura, Betul Oran, Tomasz Czerw, Ibrahim Yakoub-Agha, Wael Saber
Summary: A prognostic model was developed for myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Factors such as patient age, donor compatibility, and hemoglobin levels were found to be associated with mortality risk. The proposed scoring system could accurately predict overall survival and transplant-related mortality in two large cohorts.
Article
Hematology
Gonzalo Carreno-Tarragona, Alberto Alvarez-Larran, Claire Harrison, Jose Carlos Martinez-avila, Juan Carlos Hernandez-Boluda, Francisca Ferrer-Marin, Deepti H. Radia, Elvira Mora, Sebastian Francis, Teresa Gonzalez-Martinez, Kathryn Goddard, Manuel Perez-Encinas, Srinivasan Narayanan, Jose Maria Raya, Vikram Singh, Xabier Gutierrez, Peter Toth, Paula Amat-Martinez, Louisa Mcilwaine, Magda Alobaidi, Karan Mayani, Andrew McGregor, Ruth Stuckey, Bethan Psaila, Adrian Segura, Caroline Alvares, Kerri Davidson, Santiago Osorio, Robert Cutting, Caroline P. Sweeney, Laura Rufian, Laura Moreno, Isabel Cuenca, Jeffery Smith, Maria Luz Morales, Rodrigo Gil-Manso, Ioannis Koutsavlis, Lihui Wang, Adam J. Mead, Maria Rozman, Joaquin Martinez-Lopez, Rosa Ayala, Nicholas C. P. Cross
Summary: Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders with similar clinical presentations and outcomes. Mutational profiling revealed that both CNL and aCML have complex mutational profiles involving genes related to epigenetic regulation, splicing, and signaling pathways, with only EZH2 and TET2 differentially mutated between them. The study supports the idea that CNL and aCML are part of the same disease spectrum and highlights the importance of molecular-risk classification, particularly CSF3R mutations, in these diseases.
Article
Biophysics
Juan Carlos Hernandez-Boluda, Diderik-Jan Eikema, Linda Koster, Nicolaus Kroeger, Marie Robin, Moniek de Witte, Juergen Finke, Maria Chiara Finazzi, Annoek Broers, Ludek Raida, Nicolaas Schaap, Patrizia Chiusolo, Mareike Verbeek, Carin L. E. Hazenberg, Kazimierz Halaburda, Aleksandr Kulagin, Helene Labussiere-Wallet, Tobias Gedde-Dahl, Werner Rabitsch, Kavita Raj, Joanna Drozd-Sokolowska, Giorgia Battipaglia, Nicola Polverelli, Tomasz Czerw, Ibrahim Yakoub-Agha, Donal P. Mclornan
Summary: In this study, the outcomes of allo-HCT in 346 CALR-mutated MF patients were analyzed. The results showed that CALR-mutated patients had better overall survival rates compared to other molecular subtypes. These findings have important implications for predicting survival after transplantation in MF patients.
BONE MARROW TRANSPLANTATION
(2023)
Article
Hematology
Alexandros Rampotas, Katja Sockel, Fotios Panitsas, Catrin Theuser, Martin Bornhauser, Rafael Hernani, Juan Carlos Hernandez-Boluda, Albert Esquirol, Daniele Avenoso, Panagiotis Tsirigotis, Marie Robin, Tomasz Czerw, Grzegorz Helbig, Claire Roddie, Jonathan Lambert, Donal P. McLornan
Summary: The study retrospectively analyzed the real-world effectiveness of DLI in MF allo-HCT patients, and the results showed that DLI can achieve good responses even after relapse. However, acute graft-versus-host disease induced by DLI is a common side effect. More research is needed to determine the optimal DLI regimen and timing.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)