RESUMO
We report a patient with typical Philadelphia-chromosome-positive chronic myelocytic leukemia who developed Philadelphia-chromosome-negative acute myelocytic leukemia following autologous stem cell transplantation. The implications of this observation for disease monitoring and treatment are discussed.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Antineoplásicos/farmacologia , Benzamidas , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacologia , Pirimidinas/farmacologia , Transplante de Células-TroncoAssuntos
Citometria de Fluxo , Imunofluorescência , Leucemia Promielocítica Aguda/diagnóstico , Proteínas de Neoplasias/imunologia , Proteínas Nucleares , Fatores de Transcrição/imunologia , Humanos , Leucemia Promielocítica Aguda/genética , Proteínas de Neoplasias/genética , Proteína da Leucemia Promielocítica , Fatores de Transcrição/genética , Proteínas Supressoras de TumorRESUMO
A 40-year-old woman presented with a 2 year history of intermittent left upper quadrant pain. The clinical examination and blood tests were normal, but the pain persisted. An ultrasound scan of the abdomen revealed a hypoechoic mass in the spleen which was further investigated by computed tomography and magnetic resonance imaging (MRI). The differential diagnosis included solitary lymphoma, splenic haematoma, sarcoma, solitary metastasis or partially thrombosed splenic artery aneurysm. The patient underwent elective splenectomy and histology showed the appearance of a rare tumour. We present MRI images of this very rare splenic tumour.
RESUMO
The prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established and is of particular interest given the opportunities for targeted therapies using FLT3 inhibitors. We studied 203 patients with PML-RARA-positive APL; 43% of the patients had an FLT3 mutation (65 internal tandem duplications [ITDs], 19 D835/I836, 4 ITD+D835/I836). Both mutations were associated with higher white blood cell (WBC) count at presentation; 75% of the patients with WBC counts of 10 x 10(9)/L or greater had mutant FLT3. FLT3/ITDs were correlated with M3v subtype (P < .001), bcr3 PML breakpoint (P < .001), and expression of reciprocal RARA-PML transcripts (P = .01). Microarray analysis revealed differences in expression profiles among patients with FLT3/ITD, D835/I836, and wild-type FLT3. Patients with mutant FLT3 had a higher rate of induction death (19% vs 9%; P = .04, but no significant difference in relapse risk (28% vs 23%; P = .5) or overall survival (59% vs 67%; P = .2) at 5 years. In in vitro differentiation assays using primary APL blasts (n = 6), the FLT3 inhibitor CEP-701 had a greater effect on cell survival/proliferation in FLT3/ITD+ cells, but this inhibition was reduced in the presence of ATRA. Furthermore, in the presence of CEP-701, ATRA-induced differentiation was reduced in FLT3/ITD+ cells. These data carry implications for the use of FLT3 inhibitors as frontline therapy for APL.
Assuntos
Antineoplásicos/farmacologia , Carbazóis/farmacologia , Indóis/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Furanos , Perfilação da Expressão Gênica , Humanos , Lactente , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Análise de Sobrevida , Tretinoína/farmacologiaRESUMO
The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucleotide excision repair of chemotherapy-induced DNA damage, the efficiency of which is predicted to be affected by a lysine to glutamine variant at codon 751. We hypothesized that this constitutive genetic variant may modify clinical response to chemotherapy, and we have examined its association with outcome following chemotherapy for acute myeloid leukemia (AML) in 341 elderly patients entered into the United Kingdom Medical Research Council AML 11 trial, and with the risk of developing chemotherapy-related AML. Among subjects treated for AML, disease-free survival at one year was 44% for lysine homozygotes, compared with 36% for heterozygotes and 16% for glutamine homozygotes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.01-1.70; P = .04). Similarly, overall survival at one year was 38% for lysine homozygotes, 35% for heterozygotes, and 23% for glutamine homozygotes (HR, 1.18; 95% CI, 0.99-1.41; P = .07). Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a significantly increased risk of developing AML after chemotherapy (odds ratio, 2.22 for Gln/Gln vs Lys/Lys; 95% CI, 1.04-4.74). These data suggest that the XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy.