- [Effect of CDK Inhibitor LS-007 on Acute Lymphoblastic Leukemia and Its Mechanism]. [Journal Article]
- ZSZhongguo Shi Yan Xue Ye Xue Za Zhi 2017; 25(2):393-397
- CONCLUSIONS: LS-007 can affect the phosphorylation of RNA polymerase sites and promote cell apoptosis through changing the activities of CDK, thus having some positive significance for relieving acute lymphoblastic leukemia.
- A Case of Acute Myeloid Leukemia Concurrent With Untreated Chronic Lymphocytic Leukemia. [Case Reports]
- ALAnn Lab Med 2017; 37(4):336-338
- [Leading causes of death during the induction therapy in pediatric patients with acute lymphoblastic leukemia]. [Journal Article]
- RMRev Med Inst Mex Seguro Soc 2017 May-Jun; 55(3):286-291
- CONCLUSIONS: Early mortality was five times higher than the one reported for developed countries, while the causes of death did not differ. Close monitoring is necessary to detect and promptly treat complications secondary to chemotherapy toxicity in Mexican pediatric patients with ALL.
- Relationship between epigenetic changes in Wnt antagonists and acute leukemia. [Journal Article]
- OROncol Rep 2017; 37(5):2663-2671
- The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20me1 and the expression of tumor-suppressor genes in acute leukemia (AL) to bet...
The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20me1 and the expression of tumor-suppressor genes in acute leukemia (AL) to better understand the pathogenesis of leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls; pyrophosphate sequencing was performed to detect the methylation status of the Wnt5a promoter; and western blotting was performed to detect the overall expression levels of Wnt5a protein and histone H4K20me1 in patients with acute myeloid leukemia (AML) and in normal controls. The relationship between Wnt5a protein expression and histone H4K20me1 was analyzed. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was performed to investigate the recruitment of H4K20me1 and SET8 to the Wnt5a promoter and coding regions. Our results demonstrated that the expression levels of Wnt antagonists were generally low in AML, but showed differential expression in acute lymphocytic leukemia (ALL). In most cases of AML, methylation of the Wnt5a promoter was observed and Wnt5a protein expression was low. In some cases of AML, the overall level of H4K20me1 protein was higher than that in normal controls. In addition, Wnt5a expression was positively correlated with H4K20me1 expression and was unrelated to the methylation status of its promoter. Moreover, H4K20me1 and SET8 were enriched in the Wnt5a promoter region and coding region. By contrast, Wnt5a expression was unrelated to H4K20me1 expression in normal controls. Moreover, we observed that the methylation of Wnt antagonists was often found in patients with AL, particularly those with AML, whereas the extent of methylation was variable in ALL patients. Wnt5a expression was positively correlated with the enrichment of H4K20me1 and SET8 at the Wnt5a promoter and coding regions. H4K20me1 increased Wnt5a expression by promoting transcription initiation and elongation.
- Targeting ROR1 identifies new treatment strategies in hematological cancers. [Review]
- BSBiochem Soc Trans 2017 Apr 15; 45(2):457-464
- Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in thei...
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy. Current understanding attributes a survival role for ROR1 in cancer cells; however, its oncogenic function is cancer-type-specific and involves various signaling pathways. High interest in ROR1-targeted therapies resulted in the development of ROR1 monoclonal antibodies such as cirmtuzumab, currently in a phase I clinical trial for chronic lymphocytic leukemia. Despite these advances in translational studies, the molecular mechanism employed by ROR1 in different cancers is not yet fully understood; therefore, more insights into the oncogenic role of ROR1 signaling are crucial in order to optimize the use of targeted drugs. Recent studies provided evidence that targeting ROR1 simultaneously with inhibition of B-cell receptor (BCR) signaling is more effective in killing ROR1-positive leukemia cells, suggesting a synergistic correlation between co-targeting ROR1 and BCR pathways. Although this synergy has been previously reported for B-cell acute lymphoblastic leukemia, the molecular mechanism appears rather different. These results provide more insights into ROR1-BCR combinatorial treatment strategies in hematological malignancies, which could benefit in tailoring more effective targeted therapies in other ROR1-positive cancers.
- B-lymphocytic infiltration of the prostate to a patient with chronic lymphocytic leukemia. A case report. [Journal Article]
- AIArch Ital Urol Androl 2017 Mar 31; 89(1):83-84
- Involvement of the prostate gland, as an early extra-nodal manifestation of a hematologic disease, or as a secondary infiltration is rare. Even rarer is the acute urinary retention due to infiltratio...
Involvement of the prostate gland, as an early extra-nodal manifestation of a hematologic disease, or as a secondary infiltration is rare. Even rarer is the acute urinary retention due to infiltration by lymphocytes and simultaneously enlarged prostate. We present a case of a 61 years old male patient with a history of chronic lymphocytic leukemia, who was under oncological follow-up with no active treatment and had typical lower urinary tract symptoms due to benign prostatic hyperplasia and was receiving 5-alpha reductase inhibitor. After an acute urinary retention episode which was managed with a suprapubic catheter due to urethral catheter insertion failure, the patient was submitted to a transurethral prostatectomy. Histological examination revealed lymphocytic infiltration of the prostatic parenchyma by mostly small B cells. B-lymphocytic infiltration of the prostate gland, causes symptoms similar to benign prostatic hyperplasia. Acute urinary retention due to B-lymphocytic infiltration of the prostate is rare and the diagnosis is always histological and an oncological re-evaluation is necessary. The prognosis of these patients is related to the generalized disease rather than to the prostatic involvement.
- Molecular profiling of gene copy number abnormalities in key regulatory genes in high-risk B-lineage acute lymphoblastic leukemia: frequency and their association with clinicopathological findings in Indian patients. [Journal Article]
- MOMed Oncol 2017; 34(5):92
- Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (C...
Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL patients and their correlation with clinicopathological features by multiplex ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%) cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%) patients. Frequent genes deletions included CDNK2A/B (26%), IKZF1 (25%), PAX5 (14%), JAK2 (7%), BTG1 (6%), RB1 (5%), EBF1 (4%), ETV6 (4%), while PAR1 region genes were predominantly duplicated (20%). EBF1 deletions selectively associated with adults, IKZF1 deletions occurred frequently in high WCC and BCR-ABL1 cases, while PAR1 region gains significantly associated with MLL-AF4 cases. IKZF1 haploinsufficiency group was predominant, especially in adults (65%), high WCC (60%) patients and BCR-ABL1-negative (78%) patients. Most cases harbored multiple concurrent CNA, with IKZF1 concomitantly occurring with CDNK2A/B, PAX5 and BTG1, while JAK2 occurred with CDNK2A/B and PAX5. Mutually exclusive CNA included ETV6 and IKZF1/RB1, and EBF1 and JAK2. Our results corroborate with global reports, aggregating molecular markers in Indian HR B-ALL cases. Integration of CNA data from rapid methods like MLPA, onto background of existing gold-standard methods detecting significant chromosomal abnormalities, provides a comprehensive genetic profile in B-ALL.
- Primary fungal prophylaxis in acute leukemia patients with different risk factors: retrospective analysis from the CAESAR study. [Journal Article]
- IJInt J Hematol 2017 Apr 07
- Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factor...
Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factors is unclear. We analyzed 2015 Chinese AL patients who received a total of 2274 chemotherapy courses, including 1410 courses in acute myeloid leukemia (AML) patients and 864 courses in acute lymphocytic leukemia (ALL) patients. The IFD incidence was significantly higher among AML than ALL patients (11.8 vs. 7.1%, P < 0.001) and in patients receiving induction chemotherapy than in those receiving consolidation chemotherapy (21.6 vs. 3.7%, P < 0.001). Induction chemotherapy, decreased serum albumin, indwelling central venous catheters, parenteral nutrition, and male gender were independent risk factors for IFD in AL patients, whereas PAP independently protected against IFD development. For patients on induction chemotherapy, PAP significantly reduced IFD incidence (P < 0.001). For patients on consolidation chemotherapy, however, PAP did not significantly alter IFD incidence, although PAP did lower IFD incidence in patients with certain risk factors. PAP is highly recommended for patients on induction therapy; for those on consolidation chemotherapy, PAP should be considered for patients who present with severe neutropenia, decreased albumin, and/or an indwelling central venous catheter.
- Treatment of Philadelphia Chromosome-Positive Acute Lymphocytic Leukemia. [Review]
- CTCurr Treat Options Oncol 2017; 18(3):20
- Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine kinase inhibitors (TKIs) has ushe...
Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era, as TKIs have become the backbone of any treatment regimen for Ph+ ALL. A greater number achieve a complete remission allowing for more patients to get the transplant, although probably less patients need a transplant. For the first time in decades, there is hope for older patients with Ph+ ALL. Defining residual disease at an increasingly lower level of disease burdens termed minimal residual disease (MRD) has allowed treatment algorithms to be designed based on deep molecular responses. The aggregate of recent data suggest that this is the most important endpoint to predict for long-term outcome and to decide on the optimal post-remission approach, including transplant. Novel agents, such as blinatumumab, are likely to be incorporated into therapy for relapse and as initial therapy in an attempt to increase the number of patients who may have deep molecular responses. Many more patients with Ph+ ALL are long-term survivors, and the future is looking brighter for this group of patients.
New Search Next
- Ordinary Differential Equation Models for Adoptive Immunotherapy. [Journal Article]
- BMBull Math Biol 2017 Apr 05
- Modified T cells that have been engineered to recognize the CD19 surface marker have recently been shown to be very successful at treating acute lymphocytic leukemias. Here, we explore four previous ...
Modified T cells that have been engineered to recognize the CD19 surface marker have recently been shown to be very successful at treating acute lymphocytic leukemias. Here, we explore four previous approaches that have used ordinary differential equations to model this type of therapy, compare their properties, and modify the models to address their deficiencies. Although the four models treat the workings of the immune system in slightly different ways, they all predict that adoptive immunotherapy can be successful to move a patient from the large tumor fixed point to an equilibrium with little or no tumor.