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<p><b>OBJECTIVE</b>To screen childhood ALL related microRNAs (miRNAs), analyze association of miRNAs expression profiles with prognosis and relapse in childhood acute lymphoblastic leukemia (ALL) and explore new indicator for predicting relapse and prognosis.</p><p><b>METHODS</b>miRNAs expression profile was analyzed by gene chip in 49 newly diagnosed childhood ALL and 12 primary immune thrombocytopenia (ITP) cases (as control group). Abnormal expression of miRNAs was verified by qRT-PCR. The correlation of miRNAs expression pattern with indicators predicting early prednisone response and relapse within a year was analyzed.</p><p><b>RESULTS</b>Specific expression of miRNAs profiles associated with prednisone response and early relapse in childhood ALL was identified. Eight miRNAs (miR-18a, miR-532, miR-218, miR-625, miR-193a, miR-638, miR-550 and miR-633) could distinguish prednisone sensitive from insensitive. The early relapse of newly diagnosed patients with either high-risk or non-high-risk clinical types had some characteristics of abnormal expression of miRNAs, including miR-7, miR-216 and let-7i upregulated, while miR-486, miR-191, miR-150, miR-487 and miR-342 downregulated.</p><p><b>CONCLUSIONS</b>The initial screening reveals miRNAs differentially expressed from normal in ALL suggesting the potential roles of them in leukemogenesis. MiRNAs expression signatures may be useful for predicting prognosis and relapse in childhood ALL and directing personalized treatment.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , MicroRNAs , Genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Diagnosis , Genetics , Pathology , Prognosis , Recurrence , TranscriptomeABSTRACT
<p><b>OBJECTIVE</b>Recent studies have suggested that there is a close relation between microRNA and acute leukemia (AL). The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease.</p><p><b>METHODS</b>A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura (as control group) were enrolled in this study. Microarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA.</p><p><b>RESULTS</b>The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes (M1, M2 and M3) of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-125b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients.</p><p><b>CONCLUSIONS</b>microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Gene Expression Profiling , Leukemia, Myeloid , Classification , Genetics , Metabolism , Leukemia, Myeloid, Acute , Genetics , Metabolism , Leukemia, Promyelocytic, Acute , Genetics , Metabolism , MicroRNAs , Genetics , Metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , MetabolismABSTRACT
Objective To learn about electrolytes imbalance and water intoxication in children treated with high-dose cyclophosphamide(HD-CTX)as well as the renal function and the relative clinical symptoms,and study the mechanisms of hyponatremia.Methods Patients' clinical manifestations during and after HD-CTX therapy were summarized.Serum electrolytes and creatinine(Cr)were detected before and 6 or 8 hours after therapy with HD-CTX,antidiuretic hormone(ADH) in some patients were measured.Results Of 108 therapeutic cases 24 accompanied with vomits and 22 with a decreased urine output,in which 4 developed eyelid or ankle edema.Seven cases had neural-sarcous symptoms and 5 cases had abdominal pain or diarrhea.Serum sodium decreased significantly after HD-CTX[(139.12?3.30) mmol/L vs(134.06?8.23) mmol/L] in whom rechecked after 6 h,(141.77?3.59) mmol/L vs(133.26?6.41) mmol/L in those rechecked after 8 h(Pa0.05].Serum Cr increased 8 h after therapy[(29.95?13.61) ?mol/L vs(43.33 ? 17.25) ?mol/L P
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0.05)],which less than in control group [(4.614?1.683) IU/cm,(0.119?0.068) IU/cm,(564.2?53.8) ?m Pa