New Deletion at Promoter of HBG1 Gene in Sickle Cell Disease Patients With High HbF Level.

OBJECTIVES: The 5' upstream region of the HBG1 gene plays a very important role in the expression of fetal hemoglobin (HbF). In contrast, increased HbF levels can inhibit the deoxygenation-induced polymerization of sickle hemoglobin (α2ßS2), which leads to moderation at the clinical level among sickle cell disease (SCD) patients. Thus, we focused on this article on the study of the 5' upstream region of HBG1 among SCD pediatric patients with high levels of HbF. MATERIALS AND METHODS: Fifteen SCD pediatric patients were chosen during the first time of diagnosis, and the HbF values were determined before hydoxyurea treatment. The ages at entry ranged from 1 to 8 years. The mutational screening of the 5' upstream region of the HBG1, which extends to -587 bp, was performed by polymerase chain reaction/sequencing. RESULTS: HbF values range from 6.9% to 26%. Sequencing results showed the presence of 6 known polymorphisms, which are as follows: RS35993903, RS34844625, RS3020750, RS2860456, RS2860470, and RS12290216. Interestingly, we also found a new deletion of GCAG in the HBG1 promoter at position -273. CONCLUSIONS: We described a new mutation, which is a deletion of GCAG in the HBG1 promoter at position -273. This deletion could affect a binding site of a transcription factor unknown so far and thus modulate the expression of the HBG1 gene.

Expression of WISP3 and RhoC genes at mRNA and protein levels in inflammatory and noninflammatory breast cancer in Tunisian patients.

Previous studies have shown the expression WISP3 and RhoC in cell lines of inflammatory breast cancer (IBC). The aim in the current study was to compare the expression of both genes, in biopsy samples collected from Tunisian patients with localized or metastatic breast cancer and patients with IBC. We investigated 127 patients enrolled in Salah Azaiez Institute in Tunis. Using the RT-PCR, we showed the phenotype (WISP3-, RhoC+) is significantly associated with IBC tumors, while the (WISP3+, RhoC-)phenotype is mostly associated to non-IBC tumors. The frequencies of these tumor phenotypes are significantly different between these tumor groups (p = 10(- 7); relative risk or RR = 3.25; confidential interval or CI 95% = 1.90-5.53). Immunohistochemical test revealing the presence of WISP3 and RhoC proteins correlates with the expression in the biopsy of their encoding genes as detected by RT-PCR. In conclusion, it appears that WISP3 and RhoC genes expression status defines a molecular signature of IBC.

High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia.

Increased BMI has been correlated to an increased incidence of APL, but not to the occurrence of differentiation syndrome (DS) in APL. We consecutively treated 39 APL patients with ATRA and idarubicin (according to PETHEMA regimen). Median age was 26 years. Forty-one percent patients were classified as intermediate risk, and 59% as high risk according to Sanz's score. Thirty-three patients (85%) reached CR. Eleven of the 36 patients evaluable for DS (30.5%) developed this syndrome (severe in 7 cases, moderate in 4, and fatal in 3 cases) within a median of 12 days (range 3-23) of ATRA onset. Six of the 9 (66.6%) patients with BMI>or=30 developed DS vs. 5 of 27 (18.5%) with BMI<30 (p=0.012). Other predictors of DS in univariate analysis were: age>or=40 year (p=0.033), baseline WBC>or=20 x 10(9)/l (p=0.003), and creatinine>1.4 mg/dl (p=0.009). In multivariate analysis, BMI>or=30 remained an independent predictor of DS in addition to baseline WBC>or=20 x 10(9)/l.

Predictive factors of all-trans-retinoic acid related complications during induction therapy for acute promyelocytic leukemia.

BACKGROUND: The combination of all-trans-retinoic acid (ATRA) and chemotherapy has made acute promyelocytic leukemia (APL) a highly curable leukemia. However, several complications are reported with this treatment the most serious and life threatening being Retinoic Acid Syndrome (RAS). We aimed at identifying factors that could predict complications caused by ATRA during induction treatment of APL. PATIENTS: Forty-two patients with confirmed APL (by t(15;17) and/or PML/RARA) treated at our institution (University hospital of Tunis) between January 1998 and June 2006 using two consecutive protocols: European APL93 trial (24 patients) until February 2004 and Spanish PETHEMA LPA99 trial (18 patients) more recently. Induction regimen consisted of ATRA 45 mg/m(2)/d until CR combined to DNR 60 mg/m(2)/d x 3+Cytarabine 200 mg/m(2)/d x 7 (APL93) and Idarubicin 12 mg/m(2) d2, 4, 6, 8 (LPA99). Prednisone (0.5 mg/kg d1-d15) was added if WBC >10 x 10(9)/L to prevent RAS in LPA 99. RESULTS: Median age was 36 yr (7-64 yr), M/F=16/26 (0.61), median WBC was 2.4 x 10(9)/L (range 0.6-100 x 10(9)/L). WBC >10 x 10(9)/L was noted in 14 patients (33%). Additional cytogenetic abnormalities were seen in 12/42 (28%). Median body mass index (BMI=weight/height(2):N 20-25) was 24 kg/m(2) (range 16-40 kg/m(2)), BMI >30 was noted in nine patients (8F and 1M). Thirty-three patients achieved CR (78.57%):18/24 (75%) in APL93 versus 15/18 (83%) in LPA99. Nine patients (21.42%) had early death. Causes of early death were: RAS (6) and CNS hemorrhage (3). Complications due to ATRA were: RAS (10), Scrotal ulcerations (3), Sweet syndrome (2), Perineal ulcerations (1), and Pseudotumor cerebri (1). Prognostic factors for complications of ATRA (Fisher exact test) were: BMI >35 (p=0.055), induction treatment without cytarabine (LPA99 trial) (p=0.047), whereas age (p=0.74), gender (p=0.51), initial WBC (p=0.47), and additional cytogenetic abnormalities (p=0.83) were not predictive. Retinoic Acid Syndrome was more reported in patients with initial WBC >10 x 10(9)/L (p=0.08). CONCLUSION: We found high BMI (>35) in female and treatment without Cytarabine to increase the risk of developing complications with ATRA.