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acute lymphocytic leukemia [keywords]
- Association of -174G/C interleukin/6 gene polymorphism with the risk of chronic lymphocytic, chronic myelogenous and acute myelogenous leukemias in Turkish patients. [JOURNAL ARTICLE]
- J BUON 2014 Jul-Sept; 19(3):787-791.
Purpose: The purpose of this study was to evaluate the relationship between -174G/C interleukin-6 (IL-6) gene promoter polymorphism and susceptibility to chronic lymphocytic (CLL), chronic myelogenous (CML) and acute myelogenous leukemia (AML) in Turkish patients. Methods: The frequencies of -174G/C polymorphism were studied in 23 unrelated CLL, 25 CML and 17 AML patients and 30 healthy individuals. Single nucleotide polymorphisms (SNPs) were genotyped by the PCR-RFLP method. Results: A higher prevalence of the C allele was found in CLL, CML and AML patients. However, there were no statistically significant differences regarding either the genotype or the allelic frequencies of the -174G/C polymorphism between CLL, CML and AML cases. Conclusions: These results indicate that C allele is associated with risk of CLL, CML and AML susceptibility in Turkish patients.
- Maternal use of fertility drugs and risk of cancer in children - a nationwide population-based cohort study in Denmark. [JOURNAL ARTICLE]
- Int J Cancer 2014 Sep 25.
Large population-based studies are needed to examine the effect of maternal use of fertility drugs on the risk of cancer in children, while taking into account the effect of the underlying infertility. A cohort of 123,322 children born in Denmark between 1964 and 2006 to 68,255 women who had been evaluated for infertility was established. We used a case-cohort design and calculated hazard ratios (HRs) for cancer in childhood (0-19 years) and in young adulthood (20-29 years) associated with maternal use of six groups of fertility drugs (clomiphene, gonadotropins [i.e. human menopausal gonadotropins and follicle-stimulating hormone], gonadotropin-releasing hormone analogs, human chorionic gonadotropins, progesterone and other fertility drugs).We found no statistically significant association between maternal use of fertility drugs and risk for overall cancer in childhood or young adulthood. However, with regard to specific cancers in childhood, our results showed that maternal use of progesterone before childbirth markedly increased the risks of their offspring for acute lymphocytic leukemia (any use: HR, 4.95; 95% CI, 1.69-14.54; ≥ three cycles of use: HR, 9.96; 95% CI, 2.63-37.77) and for sympathetic nervous system tumors (any use: HR, 5.79; 95% CI, 1.23-27.24; ≥ three cycles of use: HR, 8.51; 95% CI, 1.72-42.19). These findings show that maternal use of progesterone may increase the risk for specific cancers in the offspring. Additional large epidemiological studies are urgently needed to confirm our finding. © 2014 Wiley Periodicals, Inc.
- Harnessing the immune system for cancer therapy. [JOURNAL ARTICLE]
- Curr Opin Oncol 2014 Sep 23.
Over the last 18 months, substantial progress has been made in demonstrating the clinical efficacy of harnessing the immune system to treat a variety of both solid and hematologic malignancies. This review summarizes and evaluates these seminal studies.The two treatment modalities most responsible for the success of immune based therapies in cancer are adoptive T-cell therapy and immunoregulatory antibodies. Specifically, immunotherapy is generating responses in malignancies that would otherwise have no traditional curative options such as CD19-targeted chimeric antigen receptors to treat relapsed/refractory acute lymphocytic leukemia and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and PD-1 blockade alone or in combination to treat metastatic melanoma and other solid tumors.We are at a turning point for the field of cancer immunotherapy. The scientific community is now, after decades of research, proving that these treatments have great promise for patients. Ongoing preclinical research and clinical trials over the next few years will determine the extent of impact cancer immunotherapy will have on the treatment of the general population.
- The Overexpression of KIT Proto-Oncogene in Acute Leukemic Cells Is Not Necessarily Caused by the Gene Mutation. [JOURNAL ARTICLE]
- Acta Haematol 2014 Sep 20; 133(1):116-123.
KIT is detected in a variety of cells, also in acute leukemia. Inhibition of wild-type KIT is not always satisfactory. The aim of this work was to evaluate the frequency of the most common KIT mutations in acute myeloid leukemia (AML) and determine the correlation between mutation and expression level. Samples were obtained from 75 patients with AL. CD117 presence was shown in 45 of 51 patients with AML and in 1 of 16 patients with acute lymphocytic leukemia (ALL). Asp816Val mutation was found in 3.5% of cases of AML and Val560Gly mutation in 1 sample with acute biclonal leukemia. Other genetic changes were found in 15 of 57 samples with AML: polymorphisms Met541Leu in 14% of cases, Lys546Lys in 7% and 1 case of acute biclonal leukemia, Ile798Ile in 5.3% of cases, Met541Leu in 1 acute biphenotypic leukemia and in 6.3% of ALL. Polymorphism Lys546Lys was also shown in 1 case of acute biclonal leukemia. Nonsilent genetic changes were detected in a total of 23% cases with core binding factor leukemia. There was no statistical significance between KIT expression and genetic changes. There was no correlation between the incidence and types of KIT mutations and its expression on cells in AML. © 2014 S. Karger AG, Basel.
- Cytomegalovirus appendicitis with concurrent bacteremia after chemotherapy for acute leukemia. [Journal Article]
- Korean J Intern Med 2014 Sep; 29(5):675-8.
- A Call to Action for Acute Lymphoblastic Leukemia. [JOURNAL ARTICLE]
- N Engl J Med 2014 Sep 11; 371(11):1064-1066.
The cure rates for precursor B-cell acute lymphoblastic leukemia (ALL) among children have improved, but the prognosis for older patients and children with relapsed disease remains poor. Risk stratification based on clinical features and disease characteristics can improve outcomes by enabling physicians to reduce the toxicity of therapy for patients with lower-risk disease and intensify therapy for patients with higher-risk disease. The negative prognosis associated with the t(9;22) translocation, which results in expression of the BCR-ABL1 activated kinase fusion protein, is attenuated by treatment that includes tyrosine kinase inhibitors, providing a paradigm for molecularly guided therapy in patients with precursor . . .
- Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- N Engl J Med 2014 Sep 11; 371(11):1005-15.
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults.We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL.Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6-NTRK3 fusion was sensitive to crizotinib.Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and others.).
- NRAS mutations in de novo acute leukemia: prevalence and clinical significance. [Journal Article, Research Support, Non-U.S. Gov't]
- Indian J Biochem Biophys 2014 Jun; 51(3):207-10.
The activating mutations of the Ras gene or other abnormalities in Ras signaling pathway lead to uncontrolled growth factor-independent proliferation of hematopoietic progenitors. Oncogenic mutations in NRAS gene have been observed with variable prevalence in hematopoietic malignancies. In the present study, NRAS mutations were detected using bidirectional sequencing in 264 acute leukemia cases--129 acute lymphocytic leukemia (ALL) and 135 acute myeloid leukemia (AML) and 245 age- and gender-matched controls. Missense mutation was observed only in the 12th codon of NRAS gene in 4.7% of AML and 3.16% of ALL cases. The presence of NRAS mutation did not significantly influence blast % and lactate dehydrogenase (LDH) levels in AML patients. When the data were analyzed with respect to clinical variables, the total leukocyte count was elevated for mutation positive group, compared to negative group. In AML patients with NRAS mutations, 60% failed to achieve complete remission (CR), as compared to 34.8% in mutation negative group. These results indicated that NRAS mutations might confer poor drug response. In AML, disease free survival (DFS) in NRAS mutation positive group was lesser, compared to mutation negative group (9.5 months vs. 11.68 months). In ALL patients, DFS of NRAS mutation positive group was lesser than mutation negative group (9.2 months vs. 27.5 months). The CR rate was also lower for mutation-positive patients group, compared to mutation-negative group. In conclusion, these results suggested that presence of NRAS mutation at 12th codon was associated with poor response and poorer DFS in both ALL and AML.
- Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease. [JOURNAL ARTICLE]
- Ophthal Plast Reconstr Surg 2014 Sep 4.
A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.
- Medical History, Lifestyle, Family History, and Occupational Risk Factors for Adult Acute Lymphocytic Leukemia: The InterLymph Non-Hodgkin Lymphoma Subtypes Project. [Journal Article]
- J Natl Cancer Inst Monogr 2014 Aug; 2014(48):125-9.
Acute lymphoblastic leukemia/lymphoma (ALL) in adults is a rare malignancy with a poor clinical outcome, and few reported etiologic risk factors.We performed an exploratory pooled study of 152 ALL cases and 23096 controls from 16 case-control studies to investigate the role of medical history, lifestyle, family history, and occupational risk factors and risk of ALL. Age- race/ethnicity-, sex-, and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.An increased risk of ALL was found in those with a family history of a hematological malignancy (OR = 2.6, 95% CI = 1.22 to 5.54) and in leather (OR = 3.91, 95% CI = 1.35 to 11.35) and sewing/embroidery workers (OR = 2.92, 95% CI = 1.00 to 8.49). Consumers of alcohol had an increased risk of B-cell ALL (OR = 2.87, 95% CI = 1.18 to 6.95).The small number of statistically significant risk factors identified out of the 112 variables examined could be chance findings and will require further replication to assess their role in the etiology of adult ALL.