Cases Of Acute Nonlymphocytic Leukemia Research Articles

Expressing of linc-223 and miR-125a in Patients with Acute Leukemia and Its Clinical Significance

To determine the expression level of linc-223 and miR-125a in the patients with adult acute leukemia (AL) and explore the relationship between the expression level and the occurrence, development, prognosis of leukemia. Bone marrow samples of 93 patients with AL treated in our hospital from January 2017 to September 2017 were enrolled, including 21 cases of acute lymphoblastic leukemia (ALL) and 72 cases of acute non-lymphocytic leukemia (ANLL). At the same time, bone marrow samples from 20 cases of non-malignant hematopathy patients in the same period were enrolled as control group. Real-time quantitative PCR (qRT-PCR) was used to test the expression level of linc-223 and miR-125a in bone marrow of 93 AL patients and the relationship between the level and the occurrence, development, prognosis of leukemia was analyzed. There was no significant difference in the expression of linc-223 between AL patients (ANLL and ALL) and control group (P>0.05). Moreover, there was no significant correlation between linc-223 and PML-RARα gene or the remission rate of patients after treatment. The expression of miR-125a in ANLL patients was significantly lower than those in the control group (P<0.01), but there was no significant difference between the initial treatment, recurrence and remission group (P>0.05), and also for ALL and control group (P>0.05). In the newly treatment ANLL patients, the expression level of miR-125a showed negatively correlated with LDH level and the ratio of immature cells (r=-0.454, r=-0.400), but not with sex, degree of risk, peripheral blood leukocyte count, platelet count, hemoglobin content, WT1, CRP, etc. (P>0.05). There was a positive correlation between linc-223 and miR-125a in ANLL patients (r=0.296). No abnormal expression of linc-223 was found in the bone marrow of AL patients, but miR-125a expression shows a low level and positively correlate with the expression level of linc-223 in ANLL, which is helpful for the diagnosis.

Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

BackgroundParental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated.MethodsIncident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998–2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene.ResultsPaternal smoke in the conception period was associated with AnLL (OR for ≥11 cigarettes/day = 1.79, 95% CI 1.01–3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day = 1.85, 95%CI 0.97–3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS.ConclusionsThis study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

Novel Treatment of Acute Promyelocytic Leukemia: As&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;, Retinoic Acid and Retinoid Pharmacology

Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17) chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As₂O₃ regimens as now novel therapy. Molecular gene analyses are conclusive in vivo evidence that oncogenic PML/RARa plays a crucial role in APL leukemogenesis. As a novel approach to APL treatment, one possible the action of RA, A consense sequence (5'-TCAGGTCATGACCTGA-3') has been postulated for the thyroid hormone (TRE) and retinoic acid responsive element (RARE) containing half palindromes, which located in the promoter region of target genes. High dose (100-fold) of RA-RARE-PML/RARa complex in intracellular localization appears to relieve repressor from DNA binding, including corepressors N-CoR, SMRT and HDACs, release PML/RARa- mediated transcriptional repression, and release histone deacetylase activity from PMLRARa. The resulting PML/RARa oncoprotein proteolytic degradation through the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system (UPS), as well as caspase 3 (cleavage site Asp522 within a-helics region of PML component of the fusion protein) or neutrophil elastase, or lysosomal protease enzyme induction. PML protein relocalizes into the wild-type nuclear body (PML-NB) configuration or/and wild-type RARa upregulated. An effect to relieve the blockade (inhibition) of PML/RARA-mediated RA dependent promyelocytic differentiation, and retinoic acid in APL therapy (see Figure in the full text, George Zhu, 1991). Here, like v-erbA, PML/RARa is a (strong) transcriptional repressor of the RA receptor (RAR) complex, and PML/RARa fusion receptor gene act as conditional oncogenic receptor (translocated chimeric retinoic acid a signaling) or oncogenic PML/RARa may participate in leukemogenesis of APL through blocking RA-mediated promyelocytic differentiation. This is first described in eukaryotes.

Diagnosis and outcome of neutropenic enterocolitis: experience in a single tertiary pediatric surgical center in China

Neutropenic enterocolitis (NE) is clinically defined by the triad of neutropenia, abdominal pain and fever. This retrospective study is to review 24 cases of NE in a single Chinese tertiary center, to elucidate clinical feature, treatments and outcome for this dangerous gastrointestinal complication of neutropenia. The medical records of pediatric patients who were diagnosed with neutropenic enterocolitis from 2000 to 2009 were reviewed. Of 24 cases, the ratio of male to female was 2:1, the mean age was 7.2 years. There were eight cases of acute lymphocytic leukemia, eight cases of acute non-lymphocytic leukemia, four cases of non-Hodgkin's lymphoma, one case of severe aplastic anemia, one case of neuroblastoma and two cases of simple neutropenia without underlying cause. The hematologic malignancy was significantly associated with the occurrence of NE (OR = 19.4). Seventeen cases developed NE during anticancer chemotherapy (chemo group), four cases presented with leukemia and one case presented with aplastic anemia before the initiation of chemotherapy and their presenting event leading to diagnosis. Two cases simply presented with NE without definitive reasons (no chemo group). All the patients had the typical clinical presentation, six cases had disseminated peritonitis, toxic shock, and assisted ventilations were necessary in three of these six cases. CT or ultrasound demonstrated bowel wall thickness, paucity of air in the cecum and/or right colon, pneumatosis or pneumoperitoneum. There was no difference in the nadir neutrophil count in patients, who received chemotherapy versus those who did not (P = 0.001), but the recovering time from NE in chemo group (9.3 ± 1.9) was shorter than non-chemo group (10.7 ± 5.3, P = 0.034). Sixteen (88.8%) cases have been successfully managed medically, using aggressive hemodynamic support, bowel rest, and broad-spectrum antibiotic therapy with surgical intervention reversed only for the more severe six cases (25%). Two cases died. NE is a life-threatening gastrointestinal complication of neutropenia. Physicians might remain vigilant and consider NE in any neutropenic patient rather than only in oncologic patients. It has typical clinical presentation and CT can provide clear delineation for diagnosis. Early recognition and progressed management have reduced mortality. Most children with NE may be treated without surgery with favorable outcome.

Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras, and Cbl

AbstractThe NUP98-HOXD13 (NHD13) fusion gene occurs in patients with myelodysplastic syndrome (MDS) and acute nonlymphocytic leukemia (ANLL). We reported that transgenic mice expressing NHD13 develop MDS, and that more than half of these mice eventually progress to acute leukemia. The latency period suggests a requirement for at least 1 complementary event before leukemic transformation. We conducted a candidate gene search for complementary events focused on genes that are frequently mutated in human myeloid leukemia. We investigated 22 ANLL samples and found a high frequency of Nras and Kras mutations, an absence of Npm1, p53, Runx1, Kit and Flt3 mutations, and a single Cbl mutation. Our findings support a working hypothesis that predicts that ANLL cases have one mutation which inhibits differentiation, and a complementary mutation which enhances proliferation or inhibit apoptosis. In addition, we provide the first evidence for spontaneous collaborating mutations in a genetically engineered mouse model of ANLL.

Twelve cases of malignant hematopathy treated by combined therapy of hematopoietic stem cell transplantation and Chinese herbal medicine

To evaluate the effect of hematopoietic stem cell transplantation combined with Chinese herbal medicine in treating malignant hematopathy. Allo-bone marrow transplantation (Allo-BMT) or alloperipheral blood stem cell transplantation (Allo-PBSCT), with conditioning regimen of TBI + Cy or Bu + Cy, was used to treat 4 cases of chronic granulocytic leukemia (CGL, 3 of chronic phase and 1 of acceleration phase) and one case of acute non-lymphocytic leukemia (ANLL). And auto-BMT or auto-PBSCT, with conditioning regimen of MAC or MAC + VP16, was used to treat 7 cases of hematopathy, including 5 cases of ANLL (3 of CR1 and 2 of CR2) and 2 cases of malignant lymphoma (1 of first occurring and 1 of relapse). Chinese herbal medicine was given orally to all the 12 patients after' transplantation according to TCM Syndrome Differentiation. All patients were successfully engrafted. Within the median follow-up period of 18 (4-70) months, one patient (8.3%) died of transplantation-related death, 3(25.0%) relapsed and 8 (66.7%) survived free of original disease. The transplantation effective rate was 88.8% as counting by ANLL CR1 and CGL chronic phase. Auto-BMT or auto-PBSCT in CR1 stage of acute leukemia could reduce the relapse rate, when there was no matched bone marrow donor; allo-BMT or allo-PBSCT in chronic stage could result in long-term disease-free survival of patients; Chinese herbal medicine administration in patients of malignant hematopathy might reduce the complications and plays certain role in promoting recovery of hematopoietic function.

A new case of acute nonlymphocytic leukemia (French–American–British subtype M1) with double minutes and c-MYC amplification

Herein, we present a new case of acute nonlymphocytic leukemia (ANLL) French–American–British M1 subtype with presence of multiple double minutes (dmin) derived from the amplification of the c-MYC oncogene. A review of dmins in ANLL is presented.

Distinctive AgNOR patterns of myeloid and lymphoid blasts in acute leukemia

Bone-marrow aspiration smears of 38 cases of acute leukemia (19 acute lymphoblastic leukemia, 19 acute nonlymphocytic leukemia) were stained for argyrophilic nucleolar organiser regions (AgNOR). AgNOR were assessed numerically and morphologically. There were highly significant differences in AgNOR morphology between acute lymphoblastic leukemia and acute nonlymphocytic leukemia ANLL: lymphoblast AgNORs were usually small (<3 μm) “dots/chips,” whereas myeloblasts showed larger “blebs,” or a combination of the two types (complex structures). AgNOR number was significantly less in acute lymphoblastic leukemia. In acute nonlymphocytic leukemia cases, AgNOR number also showed direct correlation with Ki67 reactivity of leukemic blasts. Am. J. Hematol. 61:149–152, 1999. © 1999 Wiley-Liss, Inc.

Distinctive AgNOR patterns of myeloid and lymphoid blasts in acute leukemia.

Bone-marrow aspiration smears of 38 cases of acute leukemia (19 acute lymphoblastic leukemia, 19 acute nonlymphocytic leukemia) were stained for argyrophilic nucleolar organiser regions (AgNOR). AgNOR were assessed numerically and morphologically. There were highly significant differences in AgNOR morphology between acute lymphoblastic leukemia and acute nonlymphocytic leukemia ANLL: lymphoblast AgNORs were usually small (<3 microm) "dots/chips," whereas myeloblasts showed larger "blebs," or a combination of the two types (complex structures). AgNOR number was significantly less in acute lymphoblastic leukemia. In acute nonlymphocytic leukemia cases, AgNOR number also showed direct correlation with Ki67 reactivity of leukemic blasts.

Childhood cancer in new zealand 1990 to 1993

An epidemiological study of childhood cancer in New Zealand identified 409 children aged 0 to 14 years with malignant neoplasms newly diagnosed between 1990 and 1993 inclusive. The original microscopic material on which the diagnoses were based was reviewed in 398 cases and the neoplasms were allocated into the 12 major groupings and 48 further subcategories of the International Classification of Childhood Cancer (ICCC). The pathology reviewers agreed with group and subcategory classification of the confirmed cancers in all but one case of acute leukemia and three cancers of the central nervous system. Changes were also made in the FAB classification of three cases of acute non-lymphocytic leukemia and in the further subcategorisation of three Hodgkin's lymphomas and ten astrocytomas. The results show a high level of diagnostic accuracy for confirmed childhood neoplasms in that time period. Nine of 15 cases of malignant melanoma notified to the study were not confirmed for various reasons, which included a change in the pathological diagnosis in four cases. Compared with Victoria (Australia), New Zealand has a high incidence rate of lymphomas in boys and an unusual female preponderance of Wilms' tumor cases.

The Philadelphia Chromosome as a Secondary Change in Leukemia: Three Case Reports and an Overview of the Literature

Three cases of acute nonlymphocytic leukemia with a Philadelphia chromosome (Ph) as a secondary abnormality are reported. The Ph was late-appearing in one patient and appeared as an additional anomaly in the other two patients. Fluorescence in situ hybridization studies of the first patient identified the presence of a minor BCR/ABL rearrangement. The findings of these cases support the conclusion that the Ph plays a role not only in leukemogenesis, but also in disease progression. An overview of the literature dealing with similar cases is also presented.

A case of acute nonlymphocytic leukemia with a derivative chromosome 5 resulting from a subtle unbalanced translocation, der(5)t(5;17)(p15.3;q25.1)

A case of acute nonlymphocytic leukemia (ANLL) is described with a previously unreported subtle unbalanced translocation, der(5)t(5;17)(p15.3;q25.1), which was confirmed and characterized by the use of fluorescence in situ hybridization (FISH).

Acute nonlymphocytic leukemia: onset after treatment for Hodgkin's disease.

This study was undertaken to examine the influence of various factors on the occurrence of acute nonlymphocytic leukemia (ANLL) in a group of longterm survivors of Hodgkin's disease (HD). From 1972 to 1992, 1045 patients with HD were assessed and treated at the Department of Radiation Oncology, the Institute of Radiology, and the Department of Human Biopathology, Hematology Section, University of Rome "La Sapienza". The average follow-up was 72 months. For a more accurate calculation of the risk of ANLL occurrence, the patients were first divided into three subgroups according to initial treatment and then according to the total treatment they had received. Moreover, to establish the probable connection between leukemia and splenic treatment the patients were also divided into three subgroups (splenectomy, splenic irradiation, and no splenectomy/no splenic irradiation). Sixteen cases of ANLL were recorded, giving an overall risk of 0.2% at 5 years and 3.4% at 20 years. In 12 patients overt leukemia was preceded by a myelodys-plastic syndrome. Five cases had evaluable chromosome analysis. Clonal chromosome abnormalities were demonstrated in two patients, whereas three patients showed an apparently normal karyotype. Bone marrow agar cultures were analyzed in two patients and were abnormal in both cases. In the radiotherapy (RT) group, the cumulative risk was 0.4% at 10 years and 3.2% at 15 and 20 years: in the chemotherapy (CT) group it was 1.2% at 10, 15, and 20 years; in the combined group it was 3.7% at 10 years and 4.9% at 15 and 20 years. In the multivariate analysis, MOPP treatment with or without RT is a statistically significant variable for ANLL occurrence (p = 0.009). This study demonstrates that splenic treatment does not lead to ANLL. Treatment with MOPP alone and with MOPP plus RT can increase the risk of ANLL.

Trisomy 8 preceding diagnosis of acute nonlymphocytic leukemia by 2 years in a patient with multiple myeloma without cytological evidence of myelodysplasia

A case of acute nonlymphocytic leukemia (ANLL) occurring 2 years after the diagnosis of multiple myeloma (MM) that had been treated by only one course of melphalan/prednisone chemotherapy is reported. Cytogenetic and fluorescence in situ hybridization analysis of peripheral blood cells revealed trisomy 8 as the sole cytogenetic defect at the time of diagnosis of ANLL. Two years earlier, when MM was diagnosed without any cytological evidence of co-existent myelodysplasia, chromosomal analysis of bone marrow cells showed the same pathological karyotype 47, XY, +8 in 14 of 20 mitoses studied. Our interpretation of this unusual cytogenetic finding is that at the time of diagnosis of MM, in spite of lacking cytological signs of myelodysplasia, an unrecognizable myelodysplastic syndrome must have been present which then evolved to ANLL.

Correlative study on the expression of p53 and DNA ploidy in acute nonlymphocytic leukemia.

We used the flow cytometric immunoassay to study the correlation between the rumor-suppressor gene product p53- and the DNA ploidy in 30 de novo cases of acute nonlymphocytic leukemia (ANLL). The results showed that 15 cases were positive expression for p53. As compared with p53 negative (p53) cases, the patients with positive p53 (p53+) had higher percentage of bone marrow blasts and lower peripheral leukocyte and platelet counts, which had no influence on the complete remission rate. Before treatment, DNA diploidy was seen in 18 cases including 12 p53- cases, and DNA aneuploidy in 12 cases including 9 p53+. After therapy, aneuploidy could be transformed into diploidy. Patients with P53+ or having aneuploidy in complete remission were at risk for early relapse. We believe that p53 may be involved in the process of leukemogenesis and progression of ANLL.

CD4 predicts nonlymphocytic lineage in acute leukemia. Insights from analysis of 125 cases using two-color flow cytometry.

The classification of acute leukemia into lymphoid or nonlymphoid is of critical therapeutic importance. Two-color flow cytometric analysis has emerged as a valuable addition to morphology and cytochemistry for the distinction of acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL). By careful selection of monoclonal antibody (mAb) combinations, diagnostic accuracy, and cost effectiveness may be enhanced compared to flow cytometry using one-color analysis. The sensitivity and specificity of a mAb panel were assessed in the determination of nonlymphocytic lineage in acute leukemia. One hundred twenty-five consecutive cases of acute leukemia were analyzed in which Wright's-stained smears, cytochemical stains, and immunophenotyping studies had been performed. The antibody panel included the nonlymphoid markers CD13, CD33, CD14, and CD4 in combination with CD2, as well as a broad panel of lymphoid and nonlineage specific markers. Of the 125 cases of acute leukemia studied, 85 cases (68%) were nonlymphocytic and 32 cases (26%) were lymphocytic (28 cases B cell, 4 cases T cell). CD13 and CD33 were very sensitive in the detection of ANLL, being expressed on 94% and 93% of ANLL cases, respectively. Sixty-five percent of cases of ANLL were CD4+ (CD2-). However, CD4+ (CD2-) had a much higher specificity (91%) for ANLL than CD13 (75%) or CD33 (84%), which were expressed in a significant number of ALL. When leukemic cells were positive for CD4 (CD2-) and either CD13 or CD33, specificity and positive predictive value (PPV) for ANLL rose to 96% and 98%, respectively. The combination of CD4 positivity with either CD13 or CD33 has higher specificity and PPV than the traditional positivity for both CD13 and CD33 (specificity 89%, PPV 96%). Careful analysis of the sensitivity, specificity, and predictive values of mAbs using this method has also allowed us to establish a more cost-effective and diagnostically relevant mAb panel. Our studies show that CD4 is underappreciated as a very specific and moderately sensitive marker for ANLL.

Adult leukemia risk and personal appliance use: a preliminary study.

The hypothesis that use of personal electric appliances may be associated with increased risk of acute nonlymphocytic leukemia in adults was tested using interview data from a previously completed case-control study of 114 cases and 133 controls conducted between 1981 and 1984. Cases were obtained from a population-based cancer registry in western Washington state, and controls were obtained from the same area by random digit dialing. Of 32 electrical home appliances for which data on use were available for adult acute nonlymphocytic leukemia cases and controls, three motor-driven personal appliances (electric razors, hair dryers, and massage units) were selected a priori because their use represents exposure to higher peak magnetic fields than that from most other home appliances. When compared on an "ever used" versus "never used" basis, use of one or more of these appliances was not associated with increased risk of leukemia in the population studied (odds ratio (OR) = 0.71, 95% confidence interval (CI) 0.41-1.24). When the appliances were considered individually, massage units were more likely to have been used by cases than by controls (OR = 3.00, 95% CI 1.43-6.32), while hair dryers were more likely to have been used by controls than cases (OR = 0.38, 95% CI 0.22-0.66). There was a nonsignificant tendency for electric razor use to differentiate the cases from controls (OR = 1.33, 95% CI 0.80-2.23). When reported daily time of use was stratified, there was no overall increased risk with increased time of use except for electric razors (p < 0.05). In addition to the analysis of appliance use data from the case-control study, the authors obtained several models of these motor-driven personal appliances and characterized the magnetic fields they produce. Magnetic field flux density, or the B-field, and spectral measurements showed that partial body exposure from such appliances may exceed 0.5 mTesla (root mean squared) at rates-of-change exceeding 10 Tesla/sec. These epidemiologic data must be interpreted cautiously because the number of cases is limited and because of proxy reporting of appliance use for deceased cases. Nevertheless, the authors believe these data indicate that peak magnetic field exposure from personal appliances warrants further investigation as a possible risk factor for acute nonlymphocytic leukemia in adults.

Translocation (16;21)(p11;q22) in acute nonlymphocytic leukemia

A case of acute nonlymphocytic leukemia (ANLL) with a translocation (16;21)(p11;q22) is presented. Clinical features of ANLL with this chromosomal change are discussed.

Tetrasomy 8 as a clonal anomaly in myeloid neoplasias

Tetrasomy of chromosome 8 as a sole anomaly is apparently extremely rare in acute non-lymphocytic leukemia (ANLL): Only two cases have been reported, one of ANLL (M5b) with this karyotype. Very recently, another case was reported of a myelodysplastic syndrome (MDS) with isolated tetrasomy 8. We report tetrasomy 8 in four cases of ANLL, two of them with M5 and one with M1 subtype. Although in the latter case, tetrasomy 8 was evident in all karyotypes analyzed, in all other cases it constituted a subpopulation of cells other than those with trisomy 8 and those with a normal karyotype (in only one case another change was evident in the karyotype). Using fluorescence in situ hybridization (FISH), the proportion of tetrasomic cells was determined in interphase nuclei. By this technique, small cell populations (3–9%) were detected in three additional trisomy cases. An additional “control” group of five trisomy cases did not show a significant population of tetrasomic interphase nuclei. The data show that tetrasomy 8, if present as a sole anomaly in ANLL, may play a rather specific role for the subtype, and probably for the progression of myeloid neoplasia as well.

子宮への浸潤が先行し，その後血液学的再燃をみた急性骨髄性白血病(M2)の1症例

子宮への浸潤が先行し，その後血液学的再燃をみた急性骨髄性白血病(M2)の1症例