AIM:To observe the expression of angiogenesis factors in the myocardial tissue of streptozotocin-induced diabetic rats .METHODS:The diabetic rat model was induced by intraperitoneal injection of streptozotocin .After 12 weeks, the cardiac function was measured by MPA cardiac function analysis system .The myocardial collagen volume fraction ( CVF) was assessed by Masson staining .The capillary vessels was quantified as the ratio of capillary to myocyte (C/M) using CD31 immunostaining.The expression levels of vascular endothelial growth factor (VEGF), angiopoietin ( Ang)-1, endostatin and Ang-2 were observed by Western blotting .RESULTS:Compared with normal control group , the left ventricular end-diastolic pressure (LVEDP) was evidently increased (P<0.01), but left ventricular pressure rise maximum rate (+dp/dtmax), left ventricular pressure decrease maximum rate (-dp/dtmax) and the ratio of capillary/myo-cyte (C/M) were significantly decreased (P<0.05).The CVF and the expression level of endostatin were significantly increased, whereas the expression levels of VEGF and Ang-1 evidently decreased (both P<0.05) in diabetic rats.Howev-er, no marked difference in the expression of Ang-2 between the 2 groups was observed (P>0.05).CONCLUSION:Im-balances between the angiogenic factors (VEGF and Ang-1) and anti-angiogenic factors (endostatin) may play an impor-tant role in the pathogenesis of diabetic cardiomyopathy .

Diabetic SD rats were established by injection of streptozotocin,and were divided into normal blood sugar control group(NC),diabetic control group(DM),and the insulin treatment group(IDM).12 weeks later,the maximum rates of increasing and decreasing pressure in left ventricle were both decreased in DM group(P＜ 0.05),and those in IDM group were higher than those in DM group(P＜0.05).Regional myocardial blood flow in DM group was lower than that in NC group [(3.39 ± 0.48 vs 3.90 ± 0.45) ml · g-1 · min-1,P＜ 0.05],and that in IDM group was higher than that in DM group [(4.46 ± 0.52 vs 3.39 ± 0.48) ml · g-1 · min-1,P＜0.05].The capillary density ratio in DM group was lower than that of NC group [0.429 ± 0.091 vs 0.545 ± 0.082,P＜0.05],but that in IDM group was higher than DM group [0.494 ± 0.076 vs 0.429 ± 0.091,P＜0.05].VEGF and Ang-1 expression in DM group were the highest in 3 groups (P＜0.05).Insulin therapy may improve the angiogenesis and myocardial blood flow in diabetic rats with cardiomyopathy.

OBJECTIVETo explore the clinical and laboratory features of chronic myeloid leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.

METHODSWe retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2), e14a2(b3a2)and e1a2 fusion transcripts negative identified by conventional real-time quantification RT-PCR (RQ-PCR). Further RQ-PCR was done with the forward primer and reverse primer designed to detect rare atypical BCR-ABL fusion genes including e14a3 and e19a2 transcripts. Direct sequencing analysis was performed on the PCR products and mutations in the BCR-ABL kinase domain were detected. The clinical data of patients were retrospectively analyzed.

RESULTSSix CML patients were found to carry t(9;22) abnormality and BCR-ABL rearrangement confirmed by FISH but classical BCR-ABL fusion genes negative detected by RQ-PCR. Further RQ-PCR and sequencing analysis confirmed the fusion of BCR exon 14 and ABL exon 3 in five CML patients (case 1-5) and the fusion of BCR exon 19 and ABL exon 2 in one CML patient (case 6). E255K and I293T IM-resistant mutations were detected in case 1 and 2, respectively. Among five cases with e14a3 transcripts, four were CML-CP, one CML-AP. Four patients were male and one was female. The median age was 48 years. The patient (case 6) with e19a2 transcripts was 40-year-old female with a diagnosis of CML-CP and PLT count was more than 1 000×10⁹/L. Imatinib (IM) therapy was administer in case 1, 2, 3, 4 and hematopoietic stem cell transplantation (HSCT) was undergone in case 5 after hydroxyurea (Hu) or interferon failure. Case 1 who had E255K IM resistant mutation, responded poorly to IM but obtained a complete cytogenetic remission (CCyR) after a substitution of dasatinib for IM. Case 2 and 3 achieved CCyR 6 months later after IM treatment and had been maintained well with IM despite I293T mutation in case 2. Case 4 attained CCyR 3 months later after IM treatment but relapsed and died soon. Case 5 was still in CCyR after HSCT. Case 6 with e19a2 transcripts got complete hematologic response after Hu treatment and CCyR was achieved soon after IM therapy.

CONCLUSIONIncidence of CML with atypical transcripts is extremely low. They could benefit from tyrosine kinase inhibitors or HSCT. Rare and atypical BCR- ABL fusion gene subtypes could be missed by conventional RQ-PCR.

Adult ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; classification ; diagnosis ; genetics ; Male ; Middle Aged ; Retrospective Studies