Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

BACKGROUND: Targeted therapy has revolutionized the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact. METHODS: Seventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed. RESULTS: Seventeen patients had blasts with the pattern of LPCs (CD34+CD38−CD58−), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+CD38−CD58− phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38−CD58− phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38− CD58− phenotype was an independent risk factor for overall survival. CONCLUSION: The presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.

Evaluation of insulin resistance and low grade inflammation in Egyptian women with subclinical hypothyroidism

Subclinical hypothyroidism [SCH] is a prevalent condition among adult population. SCH is characterized by slightly elevated serum TSH levels above the reference range and normal serum free T4 concentrations. The present study aimed to assess the association of hs-CRP [index of low grade inflammation] and insulin resistance index [HOMA-IR] in women with SCH. To achieve this goal a 26 women with SCH were enrolled in this work [age= 40.7 +/- 4.6 years] with TSH > 4.2 micro IU/ml and normal FT4, beside 20 woman. [age= 40.1 +/- 4.6SD years] as a control group. Participants with clinically apparent inflammatory thyroid diseases, any medications known to affect TSH, hs-CRP, lipid levels and insulin resistance, thyroid hormone medication up to 3 months before enrollment, pregnancy, and pituitary/hypothalamic disorders were excluded. BMI, waist circumference, FT3, FT4, hs-CRP, fasting insulin, glucose, total, HDL, LDL cholesterol, triglyceride, total cholesterol/HDL-c, LDL-c/ HDL-c ratios, HOMA-beta and HOMA-IR were determined in all participants. The mean serum levels of hs -CRP, TSH, fasting insulin, prolactin levels of subjects with SCH was higher than those of the control group [All p values = <0.05]. The SCH group had statistically non significant higher HOMA- IR values [2.1 +/- 0.4] than those of control subjects [1.9 +/- 0.3] [p=0.06]. However the mean values of serum fasting glucose, HOMA-J3, FT3, and FT4, were not differ in the 2 groups [all p values > 0.05]. There were positive correlation between insulin and hs-CRP [r=0.5, p=0.009], fasting insulin levels and TSH levels [r=043, p=0.03]. Female patients with SCH have higher serum hs-CRP level [low grade inflammation] which was associated with fasting hyperinsulinemia before obvious insulin resistance in patients with SCH. Therefore screening and early treatment for SCH may be an urge due to its adverse impacts on atherogenic indices