Evolución temporal de una línea celular leucémica que compite con la hematopoyesis saludable / Temporal evolution of a leukemic line that competes with healthy hematopoiesis

Introducción: La hipótesis del cáncer de las células madre se ha convertido en uno de los paradigmas más importantes en la investigación biomédica. Durante los últimos años se ha ido acumulando evidencia de la existencia de poblaciones similares a células madre en diferentes tipos de cáncer, especialmente en las leucemias. Objetivos: Mostrar mediante la modelación matemática y la simulación computacional cómo los cambios en los parámetros que describen las tasas de proliferación y las propiedades de autorrenovación pueden influir en la dinámica de las poblaciones de células sanas y leucémicas. Métodos: Se utilizó un modelo matemático que es una extensión de los modelos de hematopoyesis sana. Se resolvió el modelo mediante herramientas computacionales basadas en métodos numéricos, lo que permitió realizar simulaciones con diferentes parámetros e intervalos de tiempo. Resultados: Al imponer ciertas condiciones iniciales y resolver matemáticamente el modelo se obtuvo la evolución temporal de las variables de estado del sistema hematopoyético. Partiendo de un estado conocido del sistema hematopoyético se predijo el comportamiento en el tiempo de las variables de estado. Se particularizó para cuatro escenarios clínicamente relevantes. Conclusiones: El análisis del modelo dio como resultado diferentes escenarios de crecimiento de células leucémicas, entre los cuales la proliferación aumentada de células malignas es el más prominente. Sin embargo, diferentes escenarios son posibles, como la inducción de apoptosis o la autorrenovación mejorada(AU)

Introduction: The stem cell cancer hypothesis has become one of the most important paradigms in biomedical research. In recent years, evidence has accumulated for the existence of stem cell-like populations in different types of cancer, especially in leukemias. Objectives: To show, through mathematical modeling and computational simulation, how changes in the parameters that describe proliferation rates and self-renewal properties can influence the dynamics of healthy and leukemic cell populations. Methods: A mathematical model was used which is an extension of the healthy hematopoiesis models. The model was solved using computational tools based on numerical methods, this allowed to carry out countless simulations with different parameters and time intervals. Results: By imposing certain initial conditions and mathematically solving the model, the temporal evolution of the state variables of the hematopoietic system was obtained, that is, starting from a known state of the hematopoietic system, the behavior over time of the state variables of the system was predicted. It was particularized for four clinically relevant scenarios. Conclusions: The analysis of the model results in different growth scenarios of leukemic cells, among which the increased proliferation of malignant cells is the most prominent. However, different scenarios are possible, such as apoptosis induction or enhanced self-renewal(AU)

A general view of CD33⁺ leukemic stem cells and CAR-T cells as interesting targets in acute myeloblatsic leukemia therapy

Acute myeloblastic leukemia (AML) is the most frequent acute leukemia in adulthood with very poor overall survival rates. In the past few decades, significant progresses had led to the findings of new therapeutic approaches and the better understanding of the molecular complexity of this hematologic malignancy. Leukemic stem cells (LSCs) play a key role in the initiation, progression, regression, and drug resistance of different types of leukemia. The cellular and molecular characteristics of LSCs and their mechanism in the development of leukemia had not yet been specified. Therefore, determining their cellular and molecular characteristics and creating new approaches for targeted therapy of LSCs is crucial for the future of leukemia research. For this reason, the recognition of surface maker targets on the cell surface of LSCs has attracted much attention. CD33 has been detected on blasts in most AML patients, making them an interesting target for AML therapy. Genetic engineering of T cells with chimeric antigen receptor (CAR-T cell therapy) is a novel therapeutic strategy. It extends the range of antigens available for use in adoptive T-cell immunotherapy. This review will focus on CAR-T cell approaches as well as monoclonal antibody (mAB)-based therapy, the two antibody-based therapies utilized in AML treatment.

CD45 y leucemia linfoide aguda pediátrica / CD45 and childhood acute lymphoblastic leukemia

Introducción: El CD45 se expresa en las células hematopoyéticas, su determinación es indispensable para la clasificación inmunofenotípica de la leucemia linfoide aguda (LLA). Objetivo: Evaluar la expresión del antígeno CD45 en los blastos de pacientes pediátricos con LLA y su relación con las características biológicas, morfológicas y clínicas al inicio de la enfermedad, la respuesta al tratamiento y la supervivencia global (SG) de los enfermos. Métodos: Se estudiaron 160 pacientes con LLA entre diciembre del 2012 y diciembre del 2017, tratados con el protocolo ALL-IC BFM-SG 2009. El inmunofenotipaje celular de la médula ósea se realizó por citometría de flujo. Resultados: El fenotipo B CD45+ predominó en los menores de seis años de edad y en los mayores de diez, el fenotipo T CD45+. Se encontró diferencia significativa entre la ausencia de adenopatías mediastínicas, el fenotipo leucémico y la ausencia de CD45 (p=0.004); entre la respuesta a la prednisona en sangre periférica al día ocho, el fenotipo leucémico y la ausencia de CD45 (p=0.001). Se encontraron diferencias significativas entre la respuesta a la prednisona en sangre periférica el día ocho y la respuesta en médula ósea el día 33, según fenotipo leucémico (p=0.009) y la presencia en los blastos del antígeno CD45 (p=0.02). Se encontró diferencia significativa entre la SG de los enfermos, según fenotipo leucémico y la ausencia del antígeno CD45 (p=0.017). Conclusión: La expresión o ausencia del antígeno de CD45 en los blastos tiene relación con la respuesta al tratamiento y la SG de pacientes pediátricos con LLA(AU)

Introduction: CD45 is expressed in hematopoietic cells, its determination is essential for the immunophenotypic classification of acute lymphoid leukemia (ALL). Objective: To evaluate the expression of the CD45 antigen in the blasts of pediatric patients with ALL and its relationship with the biological, morphological and clinical characteristics at the onset of the disease, the response to treatment and the overall survival (OS) of the patients. Methods: 160 patients with ALL were studied between December 2012 and December 2017, treated with the ALL-IC BFM-SG 2009 protocol. Bone marrow cellular immunophenotyping was performed by flow cytometry. Results: Patients with the CD45 + B phenotype predominated in those under six years of age, while those with a CD45 + T phenotype in those older than ten. A significant difference was found between the absence of mediastinal lymph nodes, the leukemic phenotype and the absence of CD45 (p = 0.004). A significant difference was found between the response to prednisone in peripheral blood at day eight, the leukemic phenotype and the absence of CD45, p = 0.001. Significant differences were found between the response to prednisone in peripheral blood on day eight and the response in bone marrow on day 33, according to leukemic phenotype and the presence in blasts of the CD45 antigen (p = 0.009 and p = 0.02, respectively). A significant difference was found between the OS of patients, according to leukemic phenotype and the absence of the CD45 antigen, p = 0.017. Conclusion: The expression or absence of the CD45 antigen in blasts is related to the response to treatment and OS of pediatric patients with ALL(AU)

Leucemia cutis: presentación no habitual de una enfermedad conocida

RESUMEN La leucemia es una proliferación neoplásica de las células progenitoras del origen tejido hematopoyético y se conoce como leucemia cutis a toda la infiltración en de la piel por el proceso neoplásico. Se presenta el caso de una mujer de 60 años de edad con un cuadro de tres semanas de evolución de aparición de pápulas y placas eritemato-violáceas, inicialmente tratada como cuadro alérgico. Su diagnóstico final fue leucemia cutis secundaria a leucemia mieloide aguda, presentando evolución clínica tórpida.

ABSTRACT Leukemia is a neoplastic proliferation of progenitor cells of hematopoietic tissue origin and the infiltration of the neoplastic process into the skin is known as leukemia cutis. We present the case of a 60-year-old woman with a three-week history of the appearance of erythematous-violet papules and plaques, initially treated as an allergic condition. Her final diagnosis was leukemia cutis secondary to acute myeloid leukemia, presenting a torpid clinical course.

Inactivation of the NHEJ Activity of DNA-PKcs Prevents Fanconi Anemia Pre-Leukemic HSC Expansion

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure and high risk of cancer particularly leukemia. Here we show that inactivation of the non-homologous end-joining (NHEJ) activity of DNA-PKcs prevented DNA damage-induced expansion of FA pre-leukemic hematopoietic stem cells (HSCs). Furthermore, we performed serial BM transplantation to demonstrate that the DNA damage-induced expanded FA HSC compartment contained pre-leukemic stem cells that required the NHEJ activity of DNA-PKcs to induce leukemia in the secondary recipients. These results suggest that NHEJ may collaborate with FA deficiency to promote DNA damage-induced expansion of pre-leukemic HSCs.

Comparison of bioactive compounds content in leaf extracts of Passiflora incarnata, P. caerulea and P. alata and in vitro cytotoxic potential on leukemia cell lines

ABSTRACT Passiflora caerulea L., P. alata Curtis and P. incarnata L. (synonym for P. edulis Sims), are the most popular representatives of the Passiflora genus in South America. In recent years, a growing attention is paid to the biological activity and phytochemical profiles of crude extracts from various species of Passiflora in worldwide. The aim of this study was to evaluate and to compare of anti-leukemic activity of the dry crude extracts from leaves of three Passiflora species from greenhouse of Poland in two human acute lymphoblastic leukemia cell lines: CCRF-CEM and its multidrug resistant variant. Two systems of liquid chromatography in order to assessment of phytochemical composition of extracts were applied. Extracts of P. alata and P. incarnata showed the potent inhibitory activity against human acute lymphoblastic leukemia CCRF-CEM, while P. caerulea not showed activity (or activity was poor). Despite similarities in quality phytochemical profile of extracts from P. caerulea and P. incarnata, differences in quantity of chemical compounds may determine their various pharmacological potency. For the activity of P. alata extract the highest content of terpenoids and a lack of flavones C-glycosides are believed to be crucial. Summarizing, the crude extract from P. alata leaves may be considered as a substance for complementary therapy for cancer patients.

Transformación leucémica en paciente con linfoma folicular e hiperleucocitosis al diagnóstico / Leukemic transformation in a patient with follicular lymphoma and hyperleukocytosis at diagnosis

La fase leucémica como presentación de un linfoma folicular es rara y debe ser considerada factor de mal pronóstico. Por otra parte, la asociación entre linfoma folicular y síndrome mielodisplásico no se ha descrito. Se presenta el caso de una paciente en la que se detectó marcada leucocitosis y a la que se diagnosticó un linfoma folicular. Recibió quimioterapia con R-CHOP y FCR cuando recayó. Meses después, se realizó un aspirado medular en el cual se observaron cambios compatibles con mielodisplasia, únicamente recibió terapia de soporte y finalmente evolucionó a leucemia mieloide aguda. Aunque se conoce que la mielodisplasia puede ser secundaria al uso de quimioterapia, la paciente presentó además trisomía del cromosoma 11, descrita previamente en mielodisplasia y linfoma tipo Burkitt, la cual pudiera estar en relación con la evolución a leucemia mieloide aguda(AU)

Follicular lymphoma rarely presents with a leukemic phase and this should be considered a negative prognostic factor. Also, follicular lymphoma and myelodysplastic syndrome association has not been previously reported. Herein we present a patient who debuted with marked hyperleukocytosis and was diagnosed with follicular lymphoma, receiving CHOP-R and FCR after she relapsed. Several months later, secondary myelodysplastic changes were observed in her bone marrow. She received supportive therapy and finally progressed into acute myeloid leukemia. Although secondary myelodysplasia is known to be produced by chemotherapy, this patient additionally had trisomy 11, previously described in myelodysplasia and Burkitt's lymphoma, which could be linked to progression to acute myeloid leukemia(AU)

Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

Leukemic Pleural Effusion in Acute Promyelocytic Leukemia: A Case Report

In patients with acute myeloid leukemia (AML), pleural effusion may be attributed to various factors, including infection, hypoalbuminemia, and renal failure. However, leukemic infiltration of the pleural fluid is rarely reported and poorly understood. Extramedullary diseases have been reported with increasing frequency as the survival rates of patients with AML have increased. However, the reported prognostic effects of leukemic pleural effusion in patients with AML range from none to a worse prognosis. Here, we report a case of acute promyelocytic leukemia (APL) in a patient exhibiting leukemic pleural effusion with fluorescence in situ hybridization (FISH) results indicating the presence of the PML-RARA fusion gene. A 52-year-old man presented with pancytopenia, dyspnea, and fever. He had a medical history of hypertension, end-stage renal disease, and hepatitis B virus-related liver cirrhosis. A peripheral blood smear revealed the presence of multiple abnormally hypergranular promyelocytes. White blood cell differential counts were not performed due to severe pancytopenia. A bone marrow examination, immunophenotyping analysis, and cytogenetic and molecular studies revealed APL. The patient was treated with all-trans retinoic acid immediately after abnormal promyelocytes were observed in the peripheral blood smear, but induction chemotherapy was delayed because of his poor condition. His persistent dyspnea and abdominal discomfort led to a thoracentesis and the observation of abnormal promyelocytes that were positive for PML-RARA fusion gene by FISH. To our knowledge, this is the first report of leukemic pleural infiltration with PML-RARA fusion gene-positivity via FISH.

Disulfram Treatment of NUP98-PHF23 AML Is Not Effective In Vivo: Potential Role for Hematopoietic Stem Cells Niche / 임상소아혈액종양

BACKGROUND: NUP98 has numerous partner genes of which plant homeodomain (PHD) finger protein 23 (PHF23) fusion with NUP98 (NP23) can be detected by RT-PCR in patients with cytogenetically normal acute myelogenous leukemia (AML). In this fusion transcript of NP23 PHD of PHF23 is known to specifically bind H3K4me3 residues and act as a chromatic modifier. Disulfiram (DSF) which inhibits the binding of PHD to H3K4me3 residues selectively killed NP23 myeloblasts in vitro and therefore, we planned to evaluate the efficacy of DSF in vivo. METHODS: Cultured 961C cells (CD45.2), NP23 myeloblast cells were transplanted into B57BL/6 mice (CD45.1). Using limit dilution assay the number of leukemic stem cells (LSCs) could be calculated. A certain amount of 961C cells were transplanted into B57BL/6 mice and DSF was treated after 1 week. The engraftment level was monitored with CD45.2. Kaplan Meier survival curve was used to compare the survival between therapeutic and control group. RESULTS: 961C cells could be transplanted without radiation in recipient mice. Calculated LSC was estimated to be 1 out of 184 cells (95% CI range, 56–609). When treated with DSF of different doses and administration routes in 961C recipient mice no survival advantage of DSF was observed in 961C transplanted immunocompetent mouse, however it was evident that engraftment level was consistent in both groups. CONCLUSION: No survival advantage of DSF in 961C transplanted immunocompetent mouse was observed, however it was evident that 961C cells shared niche with normal hematopoietic stem cells (HSCs). We expect that 961C cells and transplanted recipient mice have the potential to be used as in vivo system for new drugs development as well as for research dealing with niche for normal HSCs and LSCs.

Death caused by ST19 Klebsiella oxytoca with wcaG virulence gene in leukemic patient / 中国人兽共患病学报

We investigated the cause of a leukemia patient induced by infect in a strain of Klebsiella oxytoca with hypermucoviscosity (HMV) phenotype.Identification and drug susceptibility of the isolate were carried out with VITEK-2 compact system.HMV phenotype was detected by string-test.The major high virulence capsular serotypes (K1,K2,K5,K20,K54 and K57) and virulence factors (rmpA,wcaG,allS,kfu,aerobactin,fimH,uge,wabG and cf29a) were detected by polymerase chain reaction and DNA sequencing.Molecular typing was performed by multilocus sequence typing (MLST).Results showed that the isolates of blood and lung tissue were Klebsiella oxytoca belonged to ST 19,which were sensitive to the antibiotics used in test,expressing the HMV phenotype.The virulence gene wcaG was found,while other virulence genes and the major high virulence capsular serotypes were negative.It indicates that ST19 Klebsiella oxytoca with wcaG virulence gene is the main reason causing leukemic patient death.

Effects of bufalin on up-regulating methylation of Wilm's tumor 1 gene in human erythroid leukemic cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells.</p><p><b>METHODS</b>The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRNA and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively.</p><p><b>RESULTS</b>The bufalin was effective to inhibit proliferation of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%±2.1% to 87.2%±5.4% with an half maximal inhibit concentration (IC) of 0.046 μmol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The proliferation index of cell cycle decreased from 76.4%±1.9% to 49.7%±1.3%. The expression levels of WT1 mRNA and its protein reduced gradually with increasing doses of bufalin, meanwhile, the methylation status of WT1 gene changed from unmethylated into partially or totally methylated. While, the expression levels of DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Bufalin can not only significantly inhibit the proliferation of HEL cells and arrest cell cycle at G/Gphase, but also induce cellular apoptosis and down-regulate the expression level of WT1. Our results provide the evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1 methylation status which is related to the up-regulation of DNMT3a and DNMT3b proteins in erythroid leukemic HEL cells.</p>

Sezary syndrome – A case report

Cutaneous T-cell lymphomas (CTCL) are a heterogenous group of lymphoproliferative disorders characterised by monoclonal expansion of malignant T cells, primarily helper T (CD4) cells. Mycosis fungoides (MF) and its erythrodermic and leukemic variant, the Sezary syndrome (SS) are the most common clinical types of CTCL. A 48 year old female presented to medical outpatient department with complaints of increasing breathlessness and cough with expectoration of six months duration. She was a known treated case of pulmonary tuberculosis. On examination she had multiple papules and rashes all over the face neck and trunk and generalized lymphadenopathy involving bilateral axillary, cervical and inguinal nodes. Due to the presence of the characteristic triad of erythroderma, lymphadenopathy and circulating atypical lymphoid cells (Sezary cells) and immunophenotypic positivity for T helper subtype, a diagnosis of Sezary syndrome was done.

Grandisin induces apoptosis in leukemic K562 cells

Abstract In this study, the potential antileukemic activity of grandisin, a lignan extracted from Piper solmsianum, was evaluated against the leukemic line K562. The cytotoxicity of grandisin (0.018 to 2.365 µM) was evaluated in K562 and normal peripheral blood lymphocytes by Trypan Blue Exclusion and MTT methods after 48h exposure to the drug. In both methods, cellular viability was concentration-dependent and the IC50 values were lower than 0.85µM. Analysis of K562 cells after treatment with grandisin showed that the cell cycle was arrested in the G1 phase with a 12.31% increase, while both S and G2 phases decreased. Morphological studies conducted after the exposure of K562 to grandisin revealed changes consistent with the apoptosis process, which was confirmed by anexin V stain and caspase activation. Thus, lignan grandisin showed antileukemic activities against the K562 cell line and the cell death process occurred via apoptosis.

Cutaneous leukemic infiltration following varicella - a case of Wolf's isotopic response

Abstract Wolf's isotopic response designates the appearance of two subsequent unrelated dermatoses in the same anatomic location. We report the case of a 51-year-old man with a medical history of chronic lymphocytic leukemia without known extra-hematopoietic involvement. The patient developed a disseminated papulo-vesiculous eruption, diagnosed as varicella. Few days after recovering, an erythematous and violaceous papular dermatosis with histopathological examination compatible with leukemic infiltration appeared on the scars of previous herpetic lesions. Complete remission was obtained under systemic corticotherapy, without cutaneous recurrence or blastic transformation. Wolf's isotopic response is attributed to a localized immunologic imbalance following a certain stimulus. In this patient, herpetic infection acted as a local spur for inaugural cutaneous leukemic infiltration, with no impact on the prognosis for the underlying disease.

Expression of E-cadherin on bone marrow mononuclear cell surface and in plasma of patients with extra-myeloid leukemia and their clinical significance / 白血病·淋巴瘤

Objective To investigate the expression and clinical significance of soluble E-cadherin (sE-cad) and E-cadherin (E-cad) in acute leukemia (AL), and to explore their relationship with the pathogenesis,development and diagnosis of extra-myeloid leukemia. Methods 87 newly diagnosed or relapsed AL patients (19 cases of L1, 29 L2, 14 M2, 20 M3, 4 M4, 1 M5) were collected from hospitalized patients in hematology department of Harbin Medical University Cancer Hospital. The plasma from 20 healthy volunteers was used as control group. The bone marrow was from 15 non-AL patients hospitalized in hematology department (7 cases of thrombocytopenic purpura, 4 iron deficiency anemia, and 4 fever). The expression of sE-cad in the plasma of 47 patients and 20 healthy volunteers was detected by ELISA; the expression of E-cad on the membrane surface of bone marrow MNC in 40 patients and 15 controls was determined by flow cytometry. Results The plasma level of sE-cad in AL group was significantly higher than that in healthy control group [(66.812±52.712) ng/ml vs. (17.976±14.206) ng/ml, P<0.01]. The plasma level of sE-cad in extra-myeloid infiltration AL group was significantly higher than that in no-extra-myeloid infiltration AL group [(83.545±60.759) ng/ml vs. (42.152±22.043) ng/ml, P<0.01]. The plasma level of sE-cad in high leukocytes AL group was higher than that in no-high leukocytes AL group [(85.166±57.828) ng/ml vs. (41.933±32.064) ng/ml, P<0.05]. The percentage of E-cad expression in AL group was significantly lower than that in control group [(13.615±14.038) % vs. (31.700±16.213) %, P<0.01]. The percentage of E-cad expression in no-extra-myeloid infiltration AL group was significantly higher than that in extra-myeloid leukemia infiltration AL group[(18.691±14.917) % vs. (6.589±8.959) %,P<0.01]. The percentage of E-cad in no-high-leukocytes AL group was significantly higher in high leukocytes AL group [(20.925±12.081) % vs. (7.446±11.118) %, P<0.01]. Conclusions The expression of E-cad on the membrane surface of bone marrow MNC and the expression of sE-cad in plasma may be closely associated with the occurrence of extra-myeloid leukemia and leukocytosis, which may be one of the important molecular mechanisms of leukemic cell infiltration and leukocytosis. High expression of sE-cad in plasma can be treated as one of index to diagnose extra-myeloid leukemia.

Relapse of Biphenotypic Acute Leukemia as a Breast Mass / 한국유방암학회지

In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia.

Protective role of vitamin E on drug-induced neuropathy.

Background: The objective of this study was to look into the protective role of vitamin E (Vit.E) on drug induced neuropathy. Methods: The study involved 18 albino rats; rats were divided into 3 Groups; Group 1 control (n = 6), Group 2 - anti leukemic drugs treated rats (n = 6), Group 3 - anti leukemic drugs and Vit.E treated rats (n = 6). Anti leukemic drugs which included vincristine (VCR), L asparaginase (L Asp), doxorubicin (ADR), prednisolone (PDN), were administered to Group 2 and Group 3 rats according to acute lymphoblastic leukemia treatment regimen (MCP841). Group 3 rats were given in addition to the anti leukemic drugs, Vit.E (100 mg/kg bodyweight/orally) daily. Tests for neuropathy were done using tail clip method, tail flick method, hot plate method on the 2nd week and tail clip method on 4th week of therapy. Results: At the end of 2nd week by tail clip method and tail flick method the mean reaction time of the anti leukemic drugs alone treated group (Group 2) was increased showing the development of neuropathy. The mean reaction time of the anti leukemic drugs + Vit.E treated group (Group 3) showed a reduction in the reaction time, showing the protective role of Vitamin E. Hot plate method done at the end of 2nd week showed a decrease in mean reaction time in Group 2 rats compared with Group 3. This could be due to the hyperthermalgesia by VCR. Group 3 was protected by Vit.E. Conclusion: Observations showed a protective role of Vit.E on drug induced neuropathy.

Microenvironment for leukemia extramedullary infiltration / 国际肿瘤学杂志

Extramedullary infiltration is one of the reasons of relapse and death for leukemia patients.Reaearches increasingly show that extramedullary microenvironment plays a pivotal role on progress and relapse of leukemia.Extramedullary infiltration of leukemia is the result of interactions among many factors and many steps,involving liver,spleen,central nervous system,thymus and other tissues and organs.