Determination of cDNA encoding BCR/ABL fusion gene in patients with chronic myelogenous leukemia using a novel FRET-based quantum dots-DNA nanosensor

2017 ◽  
Vol 966 ◽  
pp. 62-70 ◽  
Author(s):  
Mojtaba Shamsipur ◽  
Vahid Nasirian ◽  
Ali Barati ◽  
Kamran Mansouri ◽  
Asad Vaisi-Raygani ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Myelogenous Leukemia

Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2733-2740 ◽  
Author(s):  
Baijun Fang ◽  
Chunmei Zheng ◽  
Lianming Liao ◽  
Qin Han ◽  
Zhao Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Chronic Myelogenous Leukemia ◽  
Blood Cells ◽  
Fusion Gene ◽  
Fetal Liver ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Leukemic Cells

AbstractOverwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of patients with CML, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated fetal liver kinase-1–positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of 17 Philadelphia chromosome–positive (Ph+) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single-cell level. These findings provide direct evidence for the first time that rearrangement of the BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of the BCR/ABL fusion gene in both blood and endothelial cells.

scholarly journals Liposomal delivery of methylphosphonate antisense oligodeoxynucleotides in chronic myelogenous leukemia [see comments]

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 601-607 ◽  
Author(s):  
AM Tari ◽  
SD Tucker ◽  
A Deisseroth ◽  
G Lopez-Berestein
Keyword(s):  
Growth Inhibition ◽  
Cell Lines ◽  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Control Cell ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Myelogenous Leukemia ◽  
Ph Chromosome

Abstract Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by the presence of the Philadelphia (Ph) chromosome. Bcr- abl, the fusion gene associated with the Ph chromosome, expresses a p210bcr-abl protein that promotes a selective expansion of mature myeloid progenitor cells. Methylphosphonate (MP) oligodeoxynucleotides complementary to specific regions of the bcr-abl mRNA were incorporated in liposomes. We studied the effects of liposomal MP (L-MP) on the growth inhibition of CML-like cell lines. L-MP targeted to the breakpoint junctions of the bcr-abl mRNA inhibited the growth of CML cells. Fifty percent inhibition was achieved at approximately 1 mumol/L of L-MP oligonucleotide concentrations. The inhibitory effect was selective because growth inhibition was observed only with CML but not with control cell lines. Moreover, CML cell growth inhibition was dependent on the sequence of the MP oligodeoxynucleotides incorporated in the liposomes. The growth inhibition of CML cells by L-MP resulted from selective inhibition of the expression of the p210bcr-abl protein.

scholarly journals Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias

Blood ◽  
1995 ◽  
Vol 85 (8) ◽  
pp. 2162-2170 ◽  
Author(s):  
LH Leopold ◽  
SK Shore ◽  
TA Newkirk ◽  
RM Reddy ◽  
EP Reddy
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Folate Receptor ◽  
Philadelphia Chromosome ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Myeloid Leukemias ◽  
Transforming Activity ◽  
Cleavage Reactions

Chronic myelogenous leukemia is characterized by the Philadelphia chromosome, which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a novel tyrosine kinase with transforming activity. In this study, we have synthesized a multi-unti ribozyme that targets bcr-abl mRNA. In vitro ribozyme cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme compared with single or double ribozymes. The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr-abl gene (32D cells). Ribozyme transfection was accomplished either by liposomes or using follic acid-polylysine as a carrier. Multi-unit ribozyme transfection reduced the level of bcr-abl mRNA 3 logs when transfected via folate receptor-mediated uptake into transformed 32D cells. These results suggest that a multi-unit ribozyme could be an effective therapeutic agent for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia.

The Abl/bcr Fusion Gene on Chromosome 9 in Ph-Negative Chronic Myelogenous Leukemia

1998 ◽  
Vol 104 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Wei-Tong Hsu ◽  
Harvey Preisler ◽  
Katarina Szego ◽  
Rita Sprudzs ◽  
Xue-Zhi Gao
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Chromosome 9 ◽  
Myelogenous Leukemia

Determination of Imatinib in the Blood Cells of Chronic Myelogenous Leukemia Patients by Ion-Trap Mass Spectrometry

2014 ◽  
Vol 47 (6) ◽  
pp. 944-957
Author(s):  
David Potěšil ◽  
Stanislav Stejskal ◽  
Marek Borský ◽  
Pavel Šimara ◽  
Martina Havelková ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Myelogenous Leukemia ◽  
Blood Cells ◽  
Ion Trap ◽  
Myelogenous Leukemia ◽  
Ion Trap Mass Spectrometry

Detection of the BCR-ABL Fusion Gene in Natural Killer Cells in Patients with Chronic Myelogenous Leukemia

2000 ◽  
Vol 104 (2-3) ◽  
pp. 135-138 ◽  
Author(s):  
Chang-Ki Min ◽  
Il Ho Yang ◽  
Dong Wook Kim ◽  
Jong Wook Lee ◽  
Chi Wha Han ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Myelogenous Leukemia ◽  
Killer Cells

scholarly journals Relationship of bcr breakpoint to chronic phase duration, survival, and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase [see comments]

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2035-2041
Author(s):  
SW Morris ◽  
L Daniel ◽  
CM Ahmed ◽  
A Elias ◽  
P Lebowitz
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Chimeric Protein ◽  
Chronic Phase ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Phase Duration ◽  
Total Survival

Strong evidence implicates fusion of control elements and 5′ sequences of the bcr gene of chromosome 22 with 3′ sequences of the c-abl gene of chromosome 9 in the pathogenesis of Ph-positive and certain cases of Ph- negative chronic myelogenous leukemia (CML). Since this fusion gene gives rise to a chimeric tyrosine protein kinase with transforming potential, and since the bcr exon contribution to this chimeric protein is variable, the question has arisen as to whether bcr breakpoint location and bcr exon contribution could influence the clinical course of CML. Prior studies have yielded conflicting results on this point. Here we have looked, in a manner approximating a prospective analysis, at the relation of bcr breakpoint localization to the duration of chronic phase, total survival, and blast crisis phenotype in 81 patients presenting in the chronic phase of CML. We have found no significant differences in chronic phase duration or total survival among patients with breakpoints in the three major subregions of a breakpoint cluster region within the bcr gene. These findings indicate that chronic phase duration and total survival cannot be predicted from bcr breakpoint for CML patients presenting in chronic phase and suggest that unknown oncogenic events determining the onset of blast crisis are the prime determinants of prognosis. Combined analysis of blast crisis cell lineage in our patients and patients presented in a previous study has revealed an overall ratio of myeloid:lymphoid (M:L) crisis of 3.4:1, but a striking predominance of myeloid crisis in patients with breakpoints in subregion 2 (M:L of 9:1), and a lower than expected M:L ratio (1.6:1) among patients with breakpoints in subregion 3 (P for subregion 2 versus 3 = .012; subregions 0,1,2 versus 3 = .012; subregions 0,1,3 versus 2 = .032). The molecular basis for this divergence from the anticipated M:L ratio in patients with breakpoints in bcr subregions 2 and 3 is unknown.

scholarly journals Detection of Drug-Resistant Clones in Chronic Myelogenous Leukemia Patients during Dasatinib and Nilotinib Treatment

2010 ◽  
Vol 56 (3) ◽  
pp. 469-473 ◽  
Author(s):  
Franz X Gruber ◽  
Thomas Ernst ◽  
Yuri Kiselev ◽  
Andreas Hochhaus ◽  
Ingvild Mikkola
Keyword(s):  
Tyrosine Kinase ◽  
Chronic Myelogenous Leukemia ◽  
Fusion Gene ◽  
Single Step ◽  
Myelogenous Leukemia ◽  
Clinical Samples ◽  
Absolute Amount ◽  
Quantitative Monitoring ◽  
Target Template ◽  
The Absolute

AbstractBackground: Imatinib effectively inhibits the tyrosine kinase activity conferred by the BCR-ABL gene [fusion gene of BCR (breakpoint cluster region) and ABL1 (c-abl oncogene 1, receptor tyrosine kinase)] and thereby appreciably improves outcomes for chronic myelogenous leukemia (CML). A small percentage of patients relapse because of the proliferation of escape clones; such relapses can be treated with second-generation drugs. Early detection and monitoring of resistant clones may provide clinical benefit. We describe the development and testing of a new approach for quantitative monitoring of CML resistance.Methods: We designed mutation-specific assays that use hydrolysis probes and an array of allele-specific primers containing nucleotides mismatched at various positions. All assays were tested with plasmids containing corresponding mutant or wild-type sequences, allowing identification of optimal assays for specific and effective amplification of the target template. Clinical samples were then used to compare the results of selected assays with those of standard genotyping.Results: We used a modified amplification refractory mutational system approach and testing with plasmid constructs to design assays that allowed highly selective detection of resistance for all target mutations. By taking advantage of single-step performance and high PCR efficiency, we were able to quantitatively track the absolute amount of resistance conferred by a specific mutation over 4 orders of magnitude. Moreover, we designed an integrated test for dasatinib resistance that uses multiple primers simultaneously.Conclusions: These single-step, closed-tube assays specifically target mutations associated with resistance to dasatinib or nilotinib. Compared with standard genotyping, such biased genotyping improves the detection of resistance or alternative features via quantitative analysis of the absolute amount of resistance.

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