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1.
Br J Haematol ; 204(3): 892-897, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38013238

RESUMO

Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut-off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)-CMML. Five-year survival was longer for OM-CMML than for other patients (p < 0.001). Multivariate analysis identified OM-CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5-year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM-CMML. Our results support the inclusion of OM-CMML in the CMML category as a subtype with superior outcomes.


Assuntos
Leucemia Mielomonocítica Crônica , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucocitose , Prognóstico
2.
Oncologist ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349391

RESUMO

The 2022 WHO revision and the ICC classification have recently modified the diagnostic criteria for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia. However, there is no consensus on whether CMML with NPM1 mutation (NPM1mut) should be diagnosed as AML. Nowadays, it is a subject of discussion because of its diagnostic and therapeutic implications. Therefore, we describe a case of a patient diagnosed with CMML NPM1mut and briefly review the literature to highlight the uncertainty about how to classify a CMML with NPM1 mutation. We emphasize the importance of a comprehensive molecular study, which is crucial to optimize the individualized treatment of patients, enabling them to access targeted therapies.

3.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39201354

RESUMO

Two new diagnostic classifications of acute myeloid leukemia (AML) were published in 2022 to update current knowledge on disease biology. In previous 2017-edition categories of AML with myelodysplasia-related changes, AML was not otherwise specified, but AML with mutated RUNX1 experienced profound changes. We performed whole exome sequencing on a cohort of 69 patients with cytogenetic intermediate-risk AML that belonged to these diagnostic categories to correlate their mutational pattern and copy-number alterations with their new diagnostic distribution. Our results show that 45% of patients changed their diagnostic category, being AML myelodysplasia-related the most enlarged, mainly due to a high frequency of myelodysplasia-related mutations (58% of patients). These showed a good correlation with multilineage dysplasia and/or myelodysplastic syndrome history, but at the same time, 21% of de novo patients without dysplasia also presented them. RUNX1 was the most frequently mutated gene, with a high co-occurrence rate with other myelodysplasia-related mutations. We found a high prevalence of copy-neutral loss of heterozygosity, frequently inducing a homozygous state in particular mutated genes. Mild differences in current classifications explain the diagnostic disparity in 10% of patients, claiming a forthcoming unified classification.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Sequenciamento do Exoma , Leucemia Mieloide Aguda , Mutação , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Variações do Número de Cópias de DNA , Idoso de 80 Anos ou mais , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/classificação
4.
Int J Mol Sci ; 23(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35008677

RESUMO

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/genética , Neoplasias Penianas/etiologia , Neoplasias Penianas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Variações do Número de Cópias de DNA/genética , Geografia , Humanos , Masculino , Terapia de Alvo Molecular , Mutação/genética , Papillomaviridae/fisiologia , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Prognóstico , Transdução de Sinais
5.
EJHaem ; 5(5): 1014-1020, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39415899

RESUMO

The genetic landscape underlying the transformation of splenic diffuse red pulp small B-cell lymphoma (SDRPL) is not well understood. The present study aimed to unravel the genomic alterations involved in the progression and transformation of SDRPL. We performed genetic studies on both SDRPL and subsequent or synchronous diffuse large B cell lymphoma (DLBCL) samples in three SDRPL patients who eventually developed DLBCL. Our findings revealed that SDRPL cases progressing to DLBCL acquired genomic alterations in genes related to the cell cycle (CDKN2A/B, TP53, MYC and CCND3) and B cell development (BCL6).

6.
Cancers (Basel) ; 14(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36077644

RESUMO

Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

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