scholarly journals Genome‑wide profiling of lncRNA expression patterns in patients with acute promyelocytic leukemia with differentiation therapy

2018 ◽  
Author(s):  
Jian Yu ◽  
Xiao‑Ling Guo ◽  
Yuan‑Yuan Bai ◽  
Jun‑Jun Yang ◽  
Xiao‑Qun Zheng ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Expression Patterns ◽  
Promyelocytic Leukemia ◽  
Differentiation Therapy ◽  
Lncrna Expression ◽  
Genome Wide

Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome

Blood ◽  
2009 ◽  
Vol 114 (27) ◽  
pp. 5512-5521 ◽  
Author(s):  
Maaike Luesink ◽  
Jeroen L. A. Pennings ◽  
Willemijn M. Wissink ◽  
Peter C. M. Linssen ◽  
Petra Muus ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Differentiation Therapy ◽  
Chemokine Production ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Pulmonary Infiltration

Abstract In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide can induce a differentiation syndrome (DS) with massive pulmonary infiltration of differentiating leukemic cells. Because chemokines are implicated in migration and extravasation of leukemic cells, chemokines might play a role in DS. ATRA stimulation of the APL cell line NB4 induced expression of multiple CC-chemokines (CCLs) and their receptors (> 19-fold), resulting in increased chemokine levels and chemotaxis. Induction of CCL2 and CCL24 was directly mediated by ligand-activated retinoic acid receptors. In primary leukemia cells derived from APL patients at diagnosis, ATRA induced chemokine production as well. Furthermore, in plasma of an APL patient with DS, we observed chemokine induction, suggesting that chemokines might be important in DS. Dexamethasone, which efficiently reduces pulmonary chemokine production, did not inhibit chemokine induction in APL cells. Finally, chemokine production was also induced by arsenic trioxide as single agent or in combination with ATRA. We propose that differentiation therapy may induce chemokine production in the lung and in APL cells, which both trigger migration of leukemic cells. Because dexamethasone does not efficiently reduce leukemic chemokine production, pulmonary infiltration of leukemic cells may induce an uncontrollable hyperinflammatory reaction in the lung.

scholarly journals Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Zhang ◽  
Lin Wang ◽  
Fang Zheng ◽  
Ruhai Zou ◽  
Changqing Xie ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Disease Progression ◽  
Noncoding Rna ◽  
Prognostic Value ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Lncrna Expression ◽  
Genome Wide ◽  
Independent Panel ◽  
Metastatic Nasopharyngeal Carcinoma

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P=0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment.

Deregulation of RARγ and RARγ-Specific miRNAs in AML.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3182-3182
Author(s):  
Angela N. Barrett ◽  
Rajeev Gupta ◽  
Annegret Glasow ◽  
David Grimwade ◽  
Marieke von Lindern ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Acute Promyelocytic Leukemia ◽  
Cell Lines ◽  
Promyelocytic Leukemia ◽  
Differentiation Therapy ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Myeloid Progenitors

Abstract All-trans-retinoic acid (ATRA) plays important regulatory roles in hematopoiesis and is successfully used in differentiation therapy of acute promyelocytic leukemia (APL). Although ATRA effectively inhibits growth and stimulates myelomonocytic differentiation of myeloid progenitors, it is equally potent in causing expansion of multipotent hematopoietic stem cells. Results of studies utilizing mice that lack expression of a specific RAR and/or RAR subtype specific retinoids, as well as work addressing the molecular pathogenesis of acute promyelocytic leukemia (APL), indicate that the effects of ATRA on hematopoietic stem cells and myeloid progenitors are differentially mediated via the RARγ and RARα, respectively. Using qPCR we have now shown that RARγ is expressed in human cord blood derived stem cells but not in more mature myeloid progenitors or myelomonocytic cells. This change in the RARγ expression levels is paralleled by a reciprocal change in expression of RARγ specific miRNA, which we have identified and validated using multiple experimental strategies, including RARγ 3′UTR based reporter assays. RARγ is also expressed in blasts derived from non-APL AML patients (over 80% of cases examined) and AML cell lines, but is not expressed in ATRA responsive APL cell lines. The expression of RARγ miRNA, on the other hand, is markedly decreased in AML blasts when compared to the levels detected in cord blood derived CD34+ myeloid progenitor cells. Taken together our results suggest that finely tuned and miRNA mediated down-regulation of RARγ expression in the myelomonocytic lineage provides a switch from pro-proliferation to RARα mediated pro-differentiation effects of ATRA. We predict that use of a RARα specific agonist, possibly in conjunction with a strategy that negatively targets RARγ (as with RARγ selective antagonist or siRNA), would be most effective in retinoid based differentiation therapy of non APL-AML.

scholarly journals Gene expression networks underlying retinoic acid–induced differentiation of acute promyelocytic leukemia cells

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1496-1504 ◽  
Author(s):  
Ting-Xi Liu ◽  
Ji-Wang Zhang ◽  
Jiong Tao ◽  
Ruo-Bo Zhang ◽  
Qing-Hua Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Promyelocytic Leukemia ◽  
Atra Treatment ◽  
Induced Differentiation

Abstract To elucidate the molecular mechanism of all-trans-retinoic acid (ATRA)–induced differentiation of acute promyelocytic leukemia (APL) cells, the gene expression patterns in the APL cell line NB4 before and after ATRA treatment were analyzed using complementary DNA array, suppression-subtractive hybridization, and differential-display–polymerase chain reaction. A total of 169 genes, including 8 novel ones, were modulated by ATRA. The ATRA-induced gene expression profiles were in high accord with the differentiation and proliferation status of the NB4 cells. The time courses of their modulation were interesting. Among the 100 up-regulated genes, the induction of expression occurred most frequently 12-48 hours after ATRA treatment, while 59 of 69 down-regulated genes found their expression suppressed within 8 hours. The transcriptional regulation of 8 induced and 24 repressed genes was not blocked by cycloheximide, which suggests that these genes may be direct targets of the ATRA signaling pathway. A balanced functional network seemed to emerge, and it formed the foundation of decreased cellular proliferation, maintenance of cell viability, increased protein modulation, and promotion of granulocytic maturation. Several cytosolic signaling pathways, including JAKs/STAT and MAPK, may also be implicated in the symphony of differentiation.

Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid)

1991 ◽  
Vol 324 (20) ◽  
pp. 1385-1393 ◽  
Author(s):  
Raymond P. Warrell ◽  
Stanley R. Frankel ◽  
Wilson H. Miller ◽  
David A. Scheinberg ◽  
Loretta M. Itri ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Differentiation Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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