RESUMO
BACKGROUND/AIM: The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration. MATERIALS AND METHODS: Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML. RESULTS: A t(8;19)(p11;q13) was found leading to an in-frame fusion of exon 16 of the lysine acetyltransferase 6A gene (KAT6A) from 8p11 with exon 2 of the leucine twenty homeobox gene (LEUTX) from 19q13 resulting in expression of the otherwise silent LEUTX gene in the leukemic cells. The KAT6A-LEUTX protein is predicted to act as a histone acetyltransferase at its amino-terminal-KAT6A moiety but as a homeobox transcription factor at the LEUTX-carboxyl-terminal moiety. CONCLUSION: The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.
Assuntos
Biomarcadores Tumorais/genética , Quimiorradioterapia/efeitos adversos , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 8 , Fusão Gênica , Histona Acetiltransferases/genética , Proteínas de Homeodomínio/genética , Leucemia Mieloide Aguda/etiologia , Translocação Genética , Idoso , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Resultado do Tratamento , Neoplasias do Colo do Útero/terapiaRESUMO
Transdifferentiation of B cell lymphoma of germinal center cell origin to histiocytic sarcoma has recently been described but is a rare occurrence. The cause for loss of B cell differentiation in these lymphomas is unknown. We investigated whether somatic hypermutation of the PAX-5 gene, a transcription factor that is important for maintaining B cell identity and is frequently mutated in B cell lymphomas of germinal center cell origin, might be a cause for loss of PAX-5 expression and thus B cell phenotype. However, no somatic hypermutation of the PAX-5 gene was detected in the two cases we studied. The molecular basis for transdifferentiation of B cell lymphoma to histiocytic sarcoma remains therefore unresolved.
RESUMO
Granulomatous slack skin is a rare cutaneous T-lymphoproliferative disease characterized by pendulous skin folds. Histology typically reveals a dermal infiltrate of T cells and multinucleated giant cells showing elastophagocytosis. Specific genetic abnormalities have not yet been identified. Currently, granulomatous slack skin is classified according to the World Health Organization classification as a variant of mycosis fungoides although supporting genetic evidence is yet lacking. We present a well-documented case of a 46-year-old man with the typical histologic and clinical findings of granulomatous slack skin. Cytogenetic analysis of a skin biopsy revealed a t(3;9)(q12;p24) as the sole chromosomal abnormality. Fluorescence in situ hybridization analysis did not reveal involvement of the JAK2 gene, located at chromosome band 9p24, and previously shown to be amplified in Hodgkin lymphoma and primary mediastinal diffuse large B-cell lymphoma. Although more cases have to be reported and the putative oncogene involved in the translocation has yet to be identified, the cytogenetic findings are unlike those described for mycosis fungoides and suggests that granulomatous slack skin is a distinct primary cutaneous T-cell lymphoma.
Assuntos
Cromossomos Humanos Par 3 , Cromossomos Humanos Par 9 , Granuloma/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Translocação Genética , Biomarcadores Tumorais/metabolismo , Biópsia , Rearranjo Gênico/genética , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T/genética , Granuloma/genética , Granuloma/metabolismo , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Linfócitos T/patologiaRESUMO
Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently, two variants have been described with infiltration of the B-cell follicle, one variant that localizes to the marginal zone with a so-called perifollicular growth pattern, and a variant that localizes to the germinal center. These lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five similar cases of PTCL with involvement of the B-cell follicle. However, our cases differ from the cases previously described by their predominant and frequently patchy involvement of the expanded mantle zone of the B-cell follicle at onset. Later biopsies in three of the cases show diffuse infiltration of the lymph node, without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in addition to CD4. Cytogenetics was available in four of the cases but revealed no recurrent chromosomal aberrations or changes associated with other types of PTCL. No mutations of the BCL-6 gene were observed. Together, the cases seem to have an intermediately aggressive clinical behavior. Whether our cases are part of a spectrum of PTCLs that encompasses previously described variants with predominant marginal zone or germinal center infiltration or they represent a separate T-cell lymphoma type remains to be demonstrated by a study of more of such cases.
Assuntos
Linfonodos/patologia , Linfoma de Célula do Manto/patologia , Linfoma de Células T Periférico/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Antígenos CD4/metabolismo , Terapia Combinada , Proteínas de Ligação a DNA/metabolismo , Evolução Fatal , Feminino , Centro Germinativo/patologia , Humanos , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/terapia , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Indução de RemissãoRESUMO
Splenic marginal zone lymphoma (SMZL) is a lymphoma type of putative marginal zone B-cell origin. No specific genetic alterations have yet been demonstrated in SMZL. Clinically, SMZL is a low-grade B-cell non-Hodgkin lymphoma. However, the presence of p53 mutation, 7q22-7q32 deletion or the absence of somatic hypermutations of immunoglobulin genes has been correlated with a worse prognosis. In this study, we analyzed genome-wide gene expression of 24 cases of SMZL using the microarray technique. The AP-1 transcription factors c-jun, junD, junB, and c-fos as well as Notch2 were found to be specifically up-regulated. These data were confirmed by real-time PCR and immunohistochemical staining of tissue sections. The absence of concordant high expression of the MAP kinases, the signaling cascade leading to AP-1 up-regulation, suggests autoregulation of the AP-1 transcription factors and an important role in SMZL oncogenesis. High expression of Notch2, a transcription factor that induces marginal zone B-cell differentiation, is highly suggestive for a marginal zone B-cell origin of SMZL. In addition, SMZL with the 7q deletion showed high expression of TGF-beta1 and low expression of the DNA helicase XPB, a crucial part of the nucleotide excision repair complex, possibly explaining the more aggressive clinical course of those cases.