Publications by authors named "Lakshmi Sandhow"

Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model.

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Article Synopsis
  • Tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML) but do not eliminate leukemia-initiating stem cells (LSCs), leading to persistent disease and relapse.
  • The study investigates bone marrow (BM) niches in CML patients and finds differences in niche composition and function, revealing that mesenchymal stem cells from CML patients better support both normal and CML cells.
  • CXCL14 was identified as a key factor, as its loss in CML BM niches was linked to maintaining LSCs; restoring CXCL14 showed potential in inhibiting LSC growth and improving responses to TKIs like imatinib.
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Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown.

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The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP.

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Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth, but this model has never been proved.

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Despite increasing evidence for the involvement of bone marrow (BM) hematopoietic stem cell niche in leukemogenesis, how BM mesenchymal stem and progenitor cells (MSPCs) contribute to leukemia niche formation and progression remains unclear. Using an MLL-AF9 acute myeloid leukemia (AML) mouse model, we demonstrate dynamic alterations of BM cellular niche components, including MSPCs and endothelial cells during AML development and its association with AML engraftment. Primary patient AML cells also induced similar niche alterations in xenografted mice.

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Mutations of signal-induced proliferation-associated gene 1 (), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN). deficiency in mice leads to the development of age-dependent MPN. However, expression in bone marrow (BM) microenvironment and its effect on the pathogenesis of MPN remain unclear.

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White adipose tissue (WAT) expands in part through adipogenesis, a process involving fat cell generation and fatty acid (FA) storage into triglycerides (TGs). Several findings suggest that inter-individual and regional variations in adipogenesis are linked to metabolic complications. We aimed to identify cellular markers that define human adipocyte progenitors (APs) with pronounced adipogenic/TG storage ability.

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Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure.

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Aim: to validate isolation and cultivation methods of bone marrow mesenchymal stem cells (BM-MSCs) from iliac crest, and to compare biological characteristics of BM-MSCs from different age groups for preparation of autologous stem cell therapy in cartilage defect.

Methods: patients undergoing spinal surgery were selected and grouped according to age. Iliac crest bone marrow from the patients was aspirated.

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