The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukemia blasts.

Prevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.Cg- ITALIC! Prkdc (ITALIC! scid) ITALIC! Il2rg (ITALIC! tm1Wjl)/SzJ mice. CNS engraftment was seen in 23 of 29 diagnostic samples (79%): 2 of 2 from patients with overt CNS disease and 21 of 27 from patients thought to be CNS negative by diagnostic lumbar puncture. Histologic findings mimic human pathology and demonstrate that leukemic cells transit the blood-cerebrospinal fluid barrier situated close to the dural sinuses, the site of recently discovered CNS lymphatics. Retrieval of blasts from the CNS showed no evidence for chemokine receptor-mediated selective trafficking. The high frequency of infiltration and lack of selective trafficking led us to postulate that CNS tropism is a generic property of leukemic cells. To test this, we performed serial dilution experiments which showed CNS engraftment in 5 of 6 mice after transplant of as few as 10 leukemic cells. Clonal tracking techniques confirmed the polyclonal nature of CNS-infiltrating cells, with multiple clones engrafting in both the CNS and periphery. Overall, these findings suggest that subclinical seeding of the CNS is likely to be present in most BCP-ALL patients at original diagnosis, and efforts to prevent CNS relapse should concentrate on effective eradication of disease from this site rather than targeting entry mechanisms.

Cephalometric analysis of patients with beta thalassemia receiving fetal hemoglobin induction therapy.

Objective: We aimed to determine the effects of fetal hemoglobin induction therapy in restricting or even reversing the cephalometric changes associated with beta thalassemia. Materials and methods: In this comparative observational study, 90 participants were equally divided into three groups: a control group; patients with thalassemia major receiving blood transfusion (BT group); and patients receiving induction therapy (i.e., hydroxyl urea (5-10 mg/kg/day) or as much as 20 mg/kg/day) and thalidomide (2-10 mg/kg/day) along with blood transfusion (IT group). All patients underwent history taking and examination, photographic assessment, and radiographic evaluation with a lateral cephalogram. One-way ANOVA followed by post-hoc Tukey test was used to determine differences among groups. Results: The IT group differed significantly from the BT group in all photographic and skull table parameters, and most cephalometric parameters, such as facial angle (p ≤ 0.001), middle and lower facial heights (p ≤ 0.001), and inter-incisal angle (p = 0.036); the mean values in the IT group were similar to those in the control group. In-addition, dental and soft tissue measurements significantly differed among groups. For most parameters, the mean difference indicated higher values in the BT group. Conclusion: Induction therapy appeared to improve the facial angles, heights, and inter-incisal angles, whereas a class II skeletal pattern was observed in the transfusion only group. These findings suggest that fetal hemoglobin induction therapy might have restricted some of the cephalometric changes in patients with beta thalassemia.

Overexpression of Hypoxia-Inducible Factor-1α and Its Relation with Aggressiveness and Grade of Oral Squamous Cell Carcinoma.

Hypoxia-inducible factor-1α (HIF-1α) has been shown to be involved in cancer metastasis in several cancer types. There is however conflicting evidence of HIF-1α expression with oral cancer prognosis. Therefore, this study set out to investigate HIF-1α overexpression and its relationship with the aggressiveness and grade of oral squamous cell carcinoma (OSCC) and to explore the diagnostic potential of HIF-1α overexpression in OSCC in a cohort of Pakistani patients. Immunostaining of HIF-1α was performed on 54 OSCC and 14 normal oral mucosa (NOM) tissue samples and various cut-offs were used to evaluate its immunohistochemical expression. HIF-1α expression in OSCC samples was significantly higher than in controls, with minimal immunoreactivity in NOM. HIF-1α overexpression was significantly associated with increased tumor size (p = 0.046). However, no association was found between HIF-1α overexpression and increasing Broder's histological grade or TNM stage. The cut-off >10% cells with moderate to marked intensity carried a sensitivity of 70% and a specificity of 100% to distinguish between tumor and control. ROC curve analysis of HIF-1α weighted histoscores showedHIF-1α overexpression as a highly sensitive and specific diagnostic test (p < 0.001, AUC = 0.833). HIF-1α overexpression is a tumor-specific finding associated with increased tumor size and carries a potential diagnostic role.

Beta-thalassaemia trait: haematological parameters.

BACKGROUND: Beta-Thalassaemia syndromes are a group of hereditary disorders characterised by a genetic deficiency in the synthesis of beta-globin chains due to a defect in beta-globin genes. The objective of this study was to determine the haematological features of beta-thalassaemia trait (BTT). and to determine the sensitivity of Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and Mentzer Index (ML) as a screening tool for beta-thalassaemia trait. METHODS: A descriptive study was conducted in Hayatabad Medical Complex, Peshawar from May 2009 to May 2010 with 203 subjects having BTT. Blood samples were collected in EDTA anti-coagulated tubes. RBC indices were taken as part of complete blood count (CBC) by haematology analyser, and Haemoglobin (Hb) electrophoresis was done to determine the HbA2 percentage. The data was collected and analysed on statistical software for demographic details, RBC indices and HbA2 levels. RESULTS: Out of 203 patients, 92 (45%) were males and 111 (55%) were females. Most patients tested were in the 15-45 year age group. One-hundred-sixty (79%) patients had anaemia. MCV was lower than 76 fl in all the cases. Mean MCV was 59.1 fl. MCH was low, the mean MCH being 19.3 g/dl. MCH < 26 gave sensitivity of 99% in detecting BTT. We calculated MI for these cases and found out that it was < 12 in 75% of cases and < 15 in 197 (97%). CONCLUSION: Beta-thalassaemia traits present with a microcytic hypochromic blood picture, detected on simple haematology analysers as low MCV and MCH and MI which provide a useful screening tool for beta-thalassaemia trait.