Raffaella Zamponi

Advancing chemogenomic strategies for functional precision medicine in relapsed-refractory T-ALL and ETP-ALL: the GIMEMA ALL2720 trial

Luca Pagliaro, Roberto Rosati, Mariateresa Giaimo, Valentina Bardelli et autres

Despite the vast amount of cancer genomic data, linking mutations to drug efficacy remains challenging. National efforts integrating ex vivo drug response profiling (DRP) with clinical genomics are rare. To address this gap, we designed the GIMEMA ALL2720 trial (NCT04582487), a multicenter …

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Inhibition of the atypical kinase WNK1 as a therapeutic strategy in TAL-related T-cell acute lymphoblastic leukemia

Anna Montanaro, Gregorio Monica, Raffaella Zamponi, Anna D’Antuono et autres

ABSTRACT: Driver mutations in T-cell acute lymphoblastic leukemia (T-ALL) rarely affect druggable kinases. However, these kinases can be aberrantly activated or repressed as secondary oncogenic events. Thus, integrating unbiased phosphoproteomics with genomic approaches may offer novel opportunities for target discovery and therapeutic …

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Advancing Chemogenomic Strategies for Functional Precision Medicine in Relapsed/Refractory T-ALL and ETP-ALL: TheGimema ALL2720 Trial

Luca Pagliaro, Roberto Rosati, Mariateresa Giaimo, Valentina Bardelli et autres

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Disrupting the PA2G4-NPM1 axis induces nucleolar stress in NPM1c AML

Elisa Simoncini, Raffaella Zamponi, Anna Montanaro, Rosa Maria Poldi Allay Patarino et autres

Abstract Targeting NPM1, the most common abnormality in acute myeloid leukemia (AML), is still a significant challenge. Numerous efforts have focused on disrupting oligomerization, blocking nucleocytoplasmic shuttling, or promoting selective degradation of the mutant protein. Despite promising results, the clinical translation of …

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Genetics of Darier’s Disease: New Insights into Pathogenic Mechanisms

Barbara Moschella, Sabrina Busciglio, Enrico Ambrosini, Sofia Cesarini et autres

transporter. These mutations impair the intracellular calcium homeostasis leading to increased protein misfolding, endoplasmic reticulum (ER) stress response, and the activation of the unfolded protein response (UPR), culminating in keratinocyte apoptosis and anomalies in interfollicular epidermal stratification. Clinically, the disease is characterized …

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Nidogen-1, a Player in KMT2A-Rearranged Pediatric Acute Myeloid Leukemia

Jolien Vanhooren, Larissa Deneweth, Luca Pagliaro, Zhiyao Ren et autres

Despite advances in outcome, one third of children with acute myeloid leukemia (AML) relapse, and less than half will achieve long-term survival. Relapse in AML has been shown to be driven in part by leukemic stem cells (LSCs), highlighting the unmet medical …

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Ex vivo drug response profiling guides therapy in a case of high-risk acute undifferentiated leukemia with PICALM::MLLT10

Elena Mastrodicasa, Luca Pagliaro, Valentina Pierini, Valentina Bardelli et autres

: Not available.

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Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML

Matteo Marchesini, Andrea Gherli, Elisa Simoncini, Lucas Moron Dalla Tor et autres

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) …

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Linc00941 fuels ribogenesis and protein synthesis by supporting robust cMYC translation in malignant pleural mesothelioma

Mila Gugnoni, Eugenia Lorenzini, Federica Torricelli, Benedetta Donati et autres

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Myb overexpression synergizes with the loss of Pten and is a dependency factor and therapeutic target in T‐cell lymphoblastic leukemia

André Almeida, Sara T’Sas, Luca Pagliaro, Igor Fijałkowski et autres

Abstract T‐lineage acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological malignancy that accounts for 10%–15% of pediatric and 25% of adult ALL cases. Although the prognosis of T‐ALL has improved over time, the outcome of T‐ALL patients with primary resistant or relapsed …

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CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders

Luca Pagliaro, Elisa Cerretani, Anna Montanaro, Lucas Moron Dalla Tor et autres

NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). These mutations play a key role in …

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The Atypical Protein Kinase WNK1 Controls Leukemia Progression in TAL/LMO T-Cell Acute Lymphoblastic Leukemia

Anna Montanaro, Anna D’Antuono, Lucas Moron Dalla Tor, Pietro Andrei et autres

Genomic and proteomic approaches have been crucial in identifying genetic mutations and protein expression profiles underlying leukemia cell growth and survival, especially in heterogeneous diseases like T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is mainly driven by “poorly druggable” transcription factors along with …

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