RESUMO
We compared the gene expression profile of adult acute lymphoblastic leukemia (ALL) to normal hematopoietic and non-ALL samples using oligonucleotide arrays. Connective tissue growth factor (CTGF) was the highest overexpressed gene in B-cell ALL compared with the other groups, and displayed heterogeneous expression, suggesting it might have prognostic relevance. CTGF expression was examined by quantitative reverse transcriptase-polymerase chain reaction (ORT-PCR) on 79 adult ALL specimens. CTGF expression levels were significantly increased in ALL cases with B-lineage (P < .001), unfavorable cytogenetics (P < .001), and blasts expressing CD34 (P < .001). In a multivariate proportional hazards model, higher CTGF expression levels corresponded to worsening of overall survival (OS; hazard ratio 1.36, for each 10-fold increase in expression; P = .019). Further studies are ongoing to confirm the prognostic value of CTGF expression in ALL and to investigate its role in normal and abnormal lymphocyte biology.
Assuntos
Proteínas Imediatamente Precoces/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Sequência de Bases , Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidade , Estudos de Casos e Controles , Fator de Crescimento do Tecido Conjuntivo , Primers do DNA/genética , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
Increasing the upper age limit for recipients of hematopoietic stem cell transplantation (HCT) naturally has also increased the age of the corresponding related donor population. Because aging is a risk factor for malignancies, the risk of transferring preexisting malignant or premalignant hemopoietic clones in the process of HCT might be expected to increase as well. Anecdotal clinical cases of malignancies derived from donor cells in patients undergoing HCT have been published since 1971. In this article, we report 12 new cases that fit 2 different categories: (1) cases in which clones with characteristics of lymphohemopoietic malignancies were transferred from the donors to the recipients and (2) cases in which the malignant clone evolved from healthy donor cells once transplanted into the recipient. Donors in the first group were significantly older than donors in the second group. A more systematic examination of the prevalence and biology of donor malignancies would merit study.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Neoplasias Hematológicas/etiologia , Células-Tronco Neoplásicas/transplante , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores de Tecidos , Transplante Homólogo/efeitos adversos , Adulto , Fatores Etários , Idoso , Transformação Celular Neoplásica , Criança , Pré-Escolar , Células Clonais/citologia , Células Clonais/transplante , Feminino , Marcadores Genéticos , Células-Tronco Hematopoéticas/patologia , Humanos , Imunofenotipagem , Cariotipagem , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/patologia , Células Mieloides/transplante , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
The range of scientific questions utilizing DNA microarray techniques is limited by the fact that these methods require 5-40 microg of high-quality total RNA. Thus, methods that reliably amplify the starting RNA amount could expand the applicability of DNA microarray technology. We developed a single-stranded linear amplification protocol (SLAP) that combines the reproducibility of in vitro transcription and the amplification robustness of polymerase chain reactions. We compared SLAP to the NIH-IVT amplification protocol. SLAP displayed excellent conservation of the 5'/3' signal and demonstrated the most robust amplification, producing the recommended amounts of biotin-labeled RNA with as little as 0.002 microg of starting RNA. Both SLAP and NIH-IVT methods demonstrated good reproducibility, but SLAP maintained the highest level of reliability with RNA starting amounts of <0.05 microg. These results suggest that SLAP is an excellent alternative to IVT-based amplification protocols when RNA is limited by small sample size.