Assuntos
Ácidos Nucleicos Livres , Leucemia Linfocítica Crônica de Células B , Adulto , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Gravidez , Gestantes , Diagnóstico Pré-Natal , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18RESUMO
Atypical chronic myeloid leukemia (aCML) is a rare MDS/MPN disease characterized by the absence of BCR::ABL1 rearrangement and well known typical mutations associated with myeloproliferative disorders. Mutational landscape associated with this disease was recently described with frequent involvement of SETBP1 and ETNK1 mutations. CCND2 mutations have not been frequently detected in MPN or MDS/MPN patients. We describe two cases of aCML with two CCND2 mutations in 280 and 281 codons which rapidly develop progressive characteristics, and we reviewed the literature about this unfavorable association, suggesting a role as a new possible marker of aggressive disease.
Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Transtornos Mieloproliferativos , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Transtornos Mieloproliferativos/genética , Mutação , Ciclina D2/genéticaRESUMO
HLA-C*04:01:106 differs from C*04:01:01:01 by a silent nucleotide substitution in exon 4.
Assuntos
Alelos , Éxons , Antígenos HLA-C/genética , Células-Tronco Hematopoéticas , Mutação Puntual , Doadores de Tecidos , Humanos , ItáliaRESUMO
Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12Rß1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12Rß1 chain when cocultured with activated T cells or CD40L+ cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies.