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.

Impact of Gender on the Association between Low Serum Prolactin and Left Ventricular Mass in Subjects with Prediabetes

BACKGROUND: Low circulating prolactin hormone was associated with increased risk for type 2 diabetes mellitus. An inverse association of serum prolactin with cardiac remodeling was also previously suggested. Thus, the first question arises whether low serum prolactin is associated with adverse cardiac remodeling in subjects with prediabetes and if so what the impact of gender is? Second, could serum prolactin be considered a predictor of cardiac morbidity in those subjects? This study was conducted to assess prolactin level variations in relation to echocardiographic indices of cardiac remodeling among adult men and women with prediabetes. METHODS: This cross sectional study enrolled 80 subjects with prediabetic; 40 men and 40 women. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance, white blood cells count, prolactin and echocardiography were assessed. RESULTS: Prolactin was significantly lower in men than in women with prediabetes. Left ventricular mass (LVM) was significantly higher in men than in women with prediabetes. The proportion of left ventricular hypertrophy (LVH) in men with prediabetes was 45% compared with 22.5% in women (P=0.03). We also found inverse independent associations of serum prolactin with LVM and LVH in men, but not in women. CONCLUSION: In prediabetes, physiologically low serum prolactin is an independent predictor of increased LVM and LVH in adult men, but not in women. Prolactin may be a potential diagnostic biomarker for cardiac remodeling in adult men with prediabetes.