Demonstration of Interferon-α Receptors in Cultured Cell Lines and in Myeloid Cells from Patients with Acute or Chronic Myeloid Leukemia

Author(s):  
B. Möller ◽  
A. Neubauer ◽  
W. Siegert ◽  
D. Huhn
2020 ◽  
Vol 34 (3) ◽  
pp. 3773-3791 ◽  
Author(s):  
Maria Omsland ◽  
Vibeke Andresen ◽  
Stein‐Erik Gullaksen ◽  
Pilar Ayuda‐Durán ◽  
Mihaela Popa ◽  
...  

Glycobiology ◽  
2015 ◽  
Vol 26 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Silvina Laura Lompardía ◽  
Mariángeles Díaz ◽  
Daniela Laura Papademetrio ◽  
Marilina Mascaró ◽  
Matías Pibuel ◽  
...  

2003 ◽  
Vol 72 (3) ◽  
pp. 170-176 ◽  
Author(s):  
J.L. Steegmann ◽  
M.J. Requena ◽  
P. Martín-Regueira ◽  
R. de la Cámara ◽  
F. Casado ◽  
...  

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1145
Author(s):  
Anna Deregowska ◽  
Monika Pepek ◽  
Katarzyna Pruszczyk ◽  
Marcin M. Machnicki ◽  
Maciej Wnuk ◽  
...  

Telomeres are specialized nucleoprotein complexes, localized at the physical ends of chromosomes, that contribute to the maintenance of genome stability. One of the features of chronic myeloid leukemia (CML) cells is a reduction in telomere length which may result in increased genomic instability and progression of the disease. Aberrant telomere maintenance in CML is not fully understood and other mechanisms such as the alternative lengthening of telomeres (ALT) are involved. In this work, we employed five BCR-ABL1-positive cell lines, namely K562, KU-812, LAMA-84, MEG-A2, and MOLM-1, commonly used in the laboratories to study the link between mutation, copy number, and expression of telomere maintenance genes with the expression, copy number, and activity of BCR-ABL1. Our results demonstrated that the copy number and expression of BCR-ABL1 are crucial for telomere lengthening. We observed a correlation between BCR-ABL1 expression and telomere length as well as shelterins upregulation. Next-generation sequencing revealed pathogenic variants and copy number alterations in major tumor suppressors, such as TP53 and CDKN2A, but not in telomere-associated genes. Taken together, we showed that BCR-ABL1 kinase expression and activity play a crucial role in the maintenance of telomeres in CML cell lines. Our results may help to validate and properly interpret results obtained by many laboratories employing these in vitro models of CML.


Leukemia ◽  
1997 ◽  
Vol 11 (5) ◽  
pp. 667-673 ◽  
Author(s):  
FX Mahon ◽  
H Chahine ◽  
C Barbot ◽  
V Pigeonnier ◽  
B Jazwiec ◽  
...  

Leukemia ◽  
2009 ◽  
Vol 23 (11) ◽  
pp. 1999-2006 ◽  
Author(s):  
A Davies ◽  
N E Jordanides ◽  
A Giannoudis ◽  
C M Lucas ◽  
S Hatziieremia ◽  
...  

Leukemia ◽  
2003 ◽  
Vol 17 (5) ◽  
pp. 983-984 ◽  
Author(s):  
C Delfini ◽  
F Centis ◽  
L Tabellini ◽  
G Nicolini ◽  
G Visani

2011 ◽  
Vol 52 (11) ◽  
pp. 2139-2147 ◽  
Author(s):  
Carine Tang ◽  
Lisa Schafranek ◽  
Dale B. Watkins ◽  
Wendy T. Parker ◽  
Sarah Moore ◽  
...  

Leukemia ◽  
2020 ◽  
Author(s):  
Shady Adnan-Awad ◽  
Daehong Kim ◽  
Helena Hohtari ◽  
Komal Kumar Javarappa ◽  
Tania Brandstoetter ◽  
...  

Abstract The oncogenic protein Bcr-Abl has two major isoforms, p190Bcr-Abl and p210Bcr-Abl. While p210Bcr-Abl is the hallmark of chronic myeloid leukemia (CML), p190Bcr-Abl occurs in the majority of Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients. In CML, p190Bcr-Abl occurs in a minority of patients associating with distinct hematological features and inferior outcomes, yet the pathogenic role of p190Bcr-Abl and potential targeting therapies are largely uncharacterized. We employed next generation sequencing, phospho-proteomic profiling, and drug sensitivity testing to characterize p190Bcr-Abl in CML and hematopoietic progenitor cell line models (Ba/f3 and HPC-LSK). p190Bcr-Abl CML patients demonstrated poor response to imatinib and frequent mutations in epigenetic modifiers genes. In contrast with p210Bcr-Abl, p190Bcr-Abl exhibited specific transcriptional upregulation of interferon, interleukin-1 receptor, and P53 signaling pathways, associated with hyperphosphorylation of relevant signaling molecules including JAK1/STAT1 and PAK1 in addition to Src hyperphosphorylation. Comparable to p190Bcr-Abl CML patients, p190Bcr-Abl cell lines demonstrated similar transcriptional and phospho-signaling signatures. With the drug sensitivity screening we identified targeted drugs with specific activity in p190Bcr-Abl cell lines including IAP-, PAK1-, and Src inhibitors and glucocorticoids. Our results provide novel insights into the mechanisms underlying the distinct features of p190Bcr-Abl CML and promising therapeutic targets for this high-risk patient group.


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