ABSTRACT
We report one case of pediatric acute myeloid leukemia type 2 (AML-M2) who presented with karyotypic aberration of trisomy 21 with the t(5;ll) chromosomal translocation.The patient achieved complete remission after two cycles of chemotherapy of daunorubicin,cytarabine and etoposide.Then,follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46,XY.After 9 years,the patient relapsed and the karyotypic abnormalities of trisomy 21 with t(5;ll) reappeared.It was concluded that trisomy 21 with t(5;11) is a new unfavorable cytogenetic aberration in AML-M2.
ABSTRACT
DNA repair processes play a role in the development of drug resistance which represents a huge obstacle to leukemia chemotherapy.Histone H2AX phosphorylation (ser139) (γH2AX) occurs rapidly at the onset of DNA double strand break (DSB) and is critical to the regulation of DSB repair.If DNA repair is successful,cells exposed to anti-neoplastic drugs will keep entering the cycle and develop resistance to the drugs.In this study,we investigated whether γH2AX can be used as an indicator of tumor chemosensitivity and a potential target for enhancing chemotherapy.K562 and multi-drug resistant cell line K562/A02 were exposed to adriamycin (ADR) and γH2AX formed.Flow cytometry revealed that percentage of cells expressing γH2AX was increased in a dose-dependent manner and the percentage of K562/A02 cells was lower than that of K562 cells when treated with the same concentration of ADR.In order to test the potential of γH2AX to reverse drug resistance,K562/A02 cells were treated with PI3K inhibitor LY294002.It was found that LY249002 decreased ADR-induced γH2AX expression and increased the sensitivity of K562/A02 cells to ADR.Additionally,the single-cell gel electrophoresis assay and the Western blotting showed that LY249002 enhanced DSBs and decreased the expression of repair factor BRCAl.These results illustrate chemosensitivity can partly be measured by detecting γH2AX and drug resistance can be reversed by inhibiting γH2AX.
ABSTRACT
Subtelomeric rearrangements contribute to idiopathic mental retardation (MR),but most children with idiopathic MR do not show any chromosome abnormalities with standard cytogenetic analysis.The primed in situ labeling (PRINS) technique,using an oligonucleotide primer complementary to the telemetric repeat sequences (TTAGGG),can identify chromosome telomeric abnormality (deletion) in idiopathic MR children.In this study,seventy children with idiopathic MR were enrolled and subjected to PRINS.The results showed normal karyotype in all the children,subtelomeric rearrangements (1q del and 4q del) in 2 cases,which was confirmed by fluorescence in situ hybridization (FISH).It was concluded that PRINS is effective for the detection of subtelomeric rearrangements and may become a routine technique for cytogenetical abnormality screening.
ABSTRACT
Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA,which resulted in an E82K mutation.The E82K mutation co-segregated with all affected individuals in the family,and was not present in 200 normal controls.Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades.Ejection fractions were documented in 5 patients with DCM,but 4 showed a normal value of ≥50%.Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients.This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM.The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.
ABSTRACT
To investigate the role of AQP9 in brain edema,the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals.Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection,with maximum value appearing at 12 h,which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals.The further correlation analysis revealed strong positive correlations among the brain water content,the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals.These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.