NDLI: Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform

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From single cells to biology

A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal

Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform

Single-cell level co-culture platform for intercellular communication

Quantitative and dynamic assay of single cell chemotaxis

High-throughput clonal analysis of neural stem cells in microarrayed artificial niches

Migration dynamics of breast cancer cells in a tunable 3D interstitial flow chamber

The mechanical memory of lung myofibroblasts

Hyaluronic acid matrices show matrix stiffness in 2D and 3D dictates cytoskeletal order and myosin-II phosphorylation within stem cells

Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D

Growth of lung cancer cells in three-dimensional microenvironments reveals key features of tumor malignancy

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Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform

Content Provider	Royal Society of Chemistry (RSC)
Author	Copland, Mhairi Cooper, Jonathan M. Reboud, Julien Faley, Shannon
Copyright Year	2012
Abstract	The oncogenic fusion protein BCR-ABL is produced by chronic myeloid leukemia (CML) cells and functions as an abnormal, constitutively active tyrosine kinase that interferes with normal migratory and apoptotic behaviour of cells. Small molecule tyrosine kinase inhibitors (TKIs), such as dasatinib, eliminate CML progenitor cells, but fail to target the stem cell fraction resulting in persistent disease. In order to achieve a cure for CML in the majority of patients, we need an improved understanding of intracellular signalling dynamics, including the shuttling of BCR-ABL between cytosolic and nuclear compartments. In the past, the instability of BCR-ABL in assays using conventional immunohistochemical techniques has made this difficult and has not allowed for reliable analysis at the single cell level. Here we show how the utilization of rapid on-chip cell fixation within a microfluidic platform provides a means to immunofluorescently analyze the spatiotemporal localization of both BCR-ABL and c-ABL, as well as the linked apoptosis mediator, BCL-XL, in arrays of single CD34+ CML stem/progenitor cells, without cell loss. We demonstrate this proceeds up to 4 times faster than benchtop methods. Our results indicate that whilst both BCR-ABL and c-ABL shuttle from the cytoplasm to the nucleus following dasatinib treatment, the temporal dynamics are not synchronized. The microfluidic platform has the potential to provide insights into the intracellular signalling events in single cells. The ability to examine signalling events and assess BCR-ABL expression/activity in isolated cells in “real-time” may help elucidate the characteristics of rare CML stem cell events, which lead to the resistance of CML stem cells to TKIs.
Starting Page	368
Ending Page	373
Page Count	6
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	4
Issue Number	4
Journal	Integrative Biology
DOI	10.1039/c2ib00086e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	CML Fusion protein Chronic myelogenous leukemia Tyrosine kinase Dasatinib Stem cell Apoptosis Bcl-xL CD34 Cytoplasm
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors.

In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib.

Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.

Debating Frontline Therapy in Chronic Myeloid Leukemia

BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38− cells, through activation of protein kinase Cβ

Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities

Novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic myeloid leukemia stem cells

Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells

Leukemia stem cells: the root of chronic myeloid leukemia

Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform

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BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors.

In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib.

Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.

Debating Frontline Therapy in Chronic Myeloid Leukemia

BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38− cells, through activation of protein kinase Cβ

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Novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic myeloid leukemia stem cells

Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells

Leukemia stem cells: the root of chronic myeloid leukemia

Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform