Actin and tubulin of normal and leukaemic lymphocytes.
Ontology highlight
ABSTRACT:
SUBMITTER: Atkins H
PROVIDER: S-EPMC1153894 | biostudies-other | 1982 Dec
REPOSITORIES: biostudies-other
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Project description:We uncovered upregulated stem cell program in leukaemic lymphoblasts of patients with IKZF1 alterations by analyzing the archived gene-expression profiling datasets. We then used a frequent IKZF1 deletion, IK6, as a model via transduction into human primitive haematopoietic cells, followed by xenotransplantation in mice. Immunophenotypically defined stem, pro-B, and immature/mature (IM/M)-B cells were collected from primary recipients for functional assay and transcriptome profiling. Successful reconstitution in secondary recipient mice revealed the stemness of IK6+ pro-B and IM/M-B cells. Upregulated stemness and malignancy programs in IK6+ cells confirmed IK6 effects. Interestingly, these programs corresponded to distinct canonical pathways. Remarkably, the pathway profile mapped in the modelled cells well mirrored that in patients’ leukaemic cells; therefore, our study provides a seminal insight into the cancerous reprogramming of somatic cells.
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Project description:1. The pH-mobility relationships for saline-washed cells from a mouse strain of acute lymphoblastic leukaemia were examined before and after treatment with lower aldehydes, diazomethane and neuraminidase (EC 3.2.1.18). 2. The content of sialic acid released into the supernatant fluid of neuraminidase-treated cells was measured. 3. The stability of the charge-determining structures to temporary changes in environment (pH and ionic strength) was established. 4. Similar measurements were made on lymph-node cells obtained from non-leukaemic mice (a resistant and a leukaemia-susceptible strain were examined). 5. It is deduced that both the malignant and the non-malignant cell possess two dissociable acid functions at the cell surface, a carboxyl group of sialic acid and another acidic group(s), probably carboxyl, of pK 3.0-4.5. The malignant cells, however, have a basic dissociable function not present in the non-malignant types. 6. Suggestions are made as to how the difference in surface chemistry may be related to the problem of malignancy.
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