Aneuploidy identification in pre-B acute lymphoblastic leukemia patients at diagnosis by Multiplex Ligation-dependent Probe Amplification (MLPA).

Three-quarters of the patients with acute lymphoblastic leukemia (ALL), show numerical or structural chromosomal alterations, which are important factors in leukemogenesis. The use of Multiplex Ligation-dependent Probes Amplification (MLPA) has been mainly limited for searching copy number alterations of genes, suggesting that MLPA could detect numerical alterations in cancer. However, the use of MLPA in pediatrics to analyze subtelomeric sequences for aneuploidy detection has not been considered in previous studies. The aim of this study was to identify aneuploidy for the first time using MLPA and correlate the results with karyotype and DNA-index (DI), from preB ALL patients. Forty-two bone marrow samples were analyzed by cytogenetics and flow cytometry to determine the DI. The chromosomal gains and/or losses were detected by the SALSA MLPA P036 Subtelomere Mix 1 probemix®. The chromosomal number matched in 36 out of 42 samples between MLPA and karyotype (R2=0.7829, p=3.7×10-10), 18/42 between MLPA and DI (R2=0.1556, p=0.023), and 20/42 between karyotype and DI (R2=0.1509, p=0.015). MLPA results correlated with karyotype and DI. The use of MLPA led us to identify a gained marker chromosome. Our results indicate that MLPA could be a useful and fast alternative tool for aneuploidy identification in pediatric leukemia.

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia

Purpose: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). Methods: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m2/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann–Whitney U test. Results: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. Conclusions: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase (AU)

No disponible

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.

PURPOSE: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). METHODS: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. CONCLUSIONS: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.

Variantes fenotípicas menores en pacientes con leucemia linfoblástica aguda del occidente de México / Minor phenotypic variants in patients with acute lymphoblastic leukemia from west México

INTRODUCCIÓN: La leucemia linfoblástica aguda (LLA) se ha asociado a un exceso de variantes fenotípicas menores (VFM), que incluyen las variantes comunes y las anomalías menores, indicadoras de una fenogénesis alterada. El objetivo fue determinar la asociación entre VFM y LLA. PACIENTES Y MÉTODOS: Estudio de casos y controles basado en hospital de 120 niños con LLA y 120 niños sanos como grupo control, emparejados por edad y sexo, atendidos en el Hospital Civil de Guadalajara Dr. Juan I. Menchaca (México). En ambos grupos, se realizaron 28 mediciones antropométricas y la búsqueda sistemática de un listado de 405 VFM mediante un examen físico minucioso. Se estimaron las odds ratio ajustadas (ORa) con sus variables intervinientes por regresión logística. El intervalo de confianza fue del 95% (IC del 95%). RESULTADOS: Los signos antropométricos asociados con LLA fueron: segmento superior largo (ORa = 2,19; IC del 95%, 1,01-4,76), mandíbula ancha (ORa = 2,62; IC del 95%, 1,29-5,30), pabellones estrechos (ORa = 6,22, IC95%: 2,60-14,85) y teletelia (ORa = 2,53; IC del 95%m 1,07-5,98). Las VFM hipoplasia mesofacial, frente ancha, nariz pequeña, columnela corta, pabellones estrechos, teletelia, línea Sídney, pie griego y manchas café con leche (MCL) tuvieron una frecuencia de 3 a 17 veces mayor en los ninos ˜ con LLA. Por número, encontramos asociación a partir de ≥ 4 VFM (ORa = 2,14; IC del 95%, 1,25-3,66; p = 0,004). CONCLUSIONES: A partir de ≥ 4 VFM, se encontró asociación con LLA, lo que indica la existencia de factores prenatales en la fenogénesis y leucemogénesis. Confirmamos las MCL y la línea Sídney como VFM asociada a niños con LLA

INTRODUCTION: Acute lymphoblastic leukemia (ALL) has been associated with an excess of minor phenotypic variants (MPV), including common variants and minor anomalies, indicative of an altered phenogenesis. The objective of the study was to determine the association between MPV and ALL. PATIENTS AND METHODS: In a hospital based case-control study, we studied 120 children with ALL (including standard and high risk) and 120 healthy children as a control group, matched for age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made, as well as a systematic search for 405 MPV, through a physical examination. Adjusted odds ratio was estimated (aOR) with its intervening variables by logistic regression. The confidence interval was 95% (95%CI). RESULTS: Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19, 95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR= 6.22, 95%CI: 2.60- 14.85), and increase in internipple distance (aOR= 2.53, 95%CI: 1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and café-au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL. By number, an association was found from ≥4 MPV (aOR= 2.14, 95%CI: 1.25-3.66, P=.004). CONCLUSIONS: From ≥4 MPV, an association was found with ALL, suggesting prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed as MPV in children with ALL

[Minor phenotypic variants in patients with acute lymphoblastic leukemia from west Mexico]. / Variantes fenotípicas menores en pacientes con leucemia linfoblástica aguda del occidente de México.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) has been associated with an excess of minor phenotypic variants (MPV), including common variants and minor anomalies, indicative of an altered phenogenesis. The objective of the study was to determine the association between MPV and ALL. PATIENTS AND METHODS: In a hospital based case-control study, we studied 120 children with ALL (including standard and high risk) and 120 healthy children as a control group, matched for age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made, as well as a systematic search for 405 MPV, through a physical examination. Adjusted odds ratio was estimated (aOR) with its intervening variables by logistic regression. The confidence interval was 95% (95%CI). RESULTS: Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19, 95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR= 6.22, 95%CI: 2.60-14.85), and increase in internipple distance (aOR= 2.53, 95%CI: 1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and café-au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL. By number, an association was found from ≥4 MPV (aOR= 2.14, 95%CI: 1.25-3.66, P=.004). CONCLUSIONS: From ≥4 MPV, an association was found with ALL, suggesting prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed as MPV in children with ALL.