scholarly journals Clonal selection and asymmetric distribution of human leukemia in murine xenografts revealed by cellular barcoding

Blood ◽  
2017 ◽  
Vol 129 (24) ◽  
pp. 3210-3220 ◽  
Author(s):  
Mirjam E. Belderbos ◽  
Taco Koster ◽  
Bertien Ausema ◽  
Sabrina Jacobs ◽  
Sharlaine Sowdagar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clonal Selection ◽  
Asymmetric Distribution ◽  
Human Leukemia ◽  
Clone Size ◽  
Key Points ◽  
Asymmetrically Distributed ◽  
Cellular Barcoding

Key Points Patient-derived leukemia xenografts are highly polyclonal and show stochastic and clone-size–driven selection. Leukemia clones are asymmetrically distributed in xenografts and preferentially localize to the bone marrow or to extramedullary sites.

scholarly journals Establishing human leukemia xenograft mouse models by implanting human bone marrow–like scaffold-based niches

Blood ◽  
2016 ◽  
Vol 128 (25) ◽  
pp. 2949-2959 ◽  
Author(s):  
Antonella Antonelli ◽  
Willy A. Noort ◽  
Jenny Jaques ◽  
Bauke de Boer ◽  
Regina de Jong-Korlaar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Models ◽  
Risk Groups ◽  
Human Bone ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Self Renewal ◽  
Genome Wide ◽  
Key Points ◽  
Serial Transplantation

Key Points Humanized niche xenograft mouse models were generated that enabled engraftment of patients’ leukemia cells covering all risk groups. Self-renewal was better maintained in the humanized niches as determined by serial transplantation and genome-wide transcriptome studies.

scholarly journals Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 132
Author(s):  
Bruno Fattizzo ◽  
Fabio Serpenti ◽  
Wilma Barcellini ◽  
Chiara Caprioli
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Clonal Selection ◽  
Cytotoxic T Cells ◽  
Immunosuppressive Treatment ◽  
Young Patients ◽  
Suppressor Cells ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Increased Risk

Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring.

Hematological and toxicological evaluation of formaldehyde as a potential cause of human leukemia

2010 ◽  
Vol 30 (7) ◽  
pp. 725-735 ◽  
Author(s):  
Bernard D Goldstein
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Species Difference ◽  
The Body ◽  
Myelogenous Leukemia ◽  
Laboratory Animals ◽  
Human Leukemia ◽  
Toxicological Evaluation ◽  
Hematopoietic Stem ◽  
Hematological Cancers

Epidemiological findings suggesting that formaldehyde exposure is associated with a higher risk of acute myelogenous leukemia (AML) and other hematological cancers have led to consideration of the potential mechanism of action by which inhalation of this rapidly reactive agent can cause bone marrow cancer. Two major mechanism-based arguments against formaldehyde as a leukemogen have been the difficulty in envisioning how inhaled formaldehyde might penetrate to the bone marrow; and the lack of similarity of non-cancer effects to other known human myeloleukemogens, particularly the absence of pancytopenia in humans or laboratory animals exposed to high levels. However, both of these arguments have been addressed by the recent finding of a pancytopenic effect and chromosomal abnormalities in heavily exposed Chinese workers which, if replicated, are indicative of a genotoxic effect of formaldehyde on hematopoietic stem cells that is in keeping with other known human leukemogens. Review of the body of evidence suggests an apparent discrepancy between studies in laboratory animals, which generally fail to show evidence of penetration of formaldehyde into the blood or evidence of blood or bone marrow genotoxicity, and studies of exposed humans in which there tends to be evidence of genotoxicity in circulating blood cells. One possible explanation for this discrepancy is species difference. Another possible explanation is that myeloid precursors within the nasal mucosa may be the site for leukemogenesis. However, chloromas, which are local collections of myeloid tumor cells, are rarely if ever found in the nose. Other proposed mechanisms for formaldehyde leukemogenesis are reviewed, and dose issues at the interface between the epidemiological and hematotoxicological findings are explored.

scholarly journals PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3609-3617 ◽  
Author(s):  
Jinjun Dang ◽  
Lei Wei ◽  
Jeroen de Ridder ◽  
Xiaoping Su ◽  
Alistair G. Rust ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Suppressor ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
Human Leukemia ◽  
Key Points ◽  
Leukemia Development ◽  
Common Target ◽  
Mouse Mutagenesis

Key Points Heterozygous alterations of Pax5, the most common target of genetic alteration in ALL, promote ALL in mouse mutagenesis models. Leukemia development is accompanied by the acquisition of genetic alterations commonly observed in human leukemia.

scholarly journals AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model

Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. e90-e97 ◽  
Author(s):  
Mark Wunderlich ◽  
Benjamin Mizukawa ◽  
Fu-Sheng Chou ◽  
Christina Sexton ◽  
Mahesh Shrestha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Bone Marrow Cells ◽  
Xenograft Model ◽  
Chemotherapy Treatment ◽  
Key Points ◽  
Increased Sensitivity ◽  
Total Bone Marrow ◽  
Marrow Cells

Key Points A relevant xenograft chemotherapy model was developed by using standard AML induction therapy drugs and primary human AML patient samples. Human AML cells show significantly increased sensitivity to in vivo chemotherapy treatment compared with murine LSK and total bone marrow cells.

scholarly journals Nonhuman primates express human leukemia-associated antigens

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1074-1078
Author(s):  
JM Pesando ◽  
TA Conrad
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Lymphoblastic Leukemia ◽  
Adherent Cell ◽  
Human Leukemia ◽  
Papio Cynocephalus ◽  
Normal Tissues ◽  
Leukemia Antigen

Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.

Multimodal imaging reveals structural and functional heterogeneity in different bone marrow compartments: functional implications on hematopoietic stem cells

Blood ◽  
2013 ◽  
Vol 122 (10) ◽  
pp. 1730-1740 ◽  
Author(s):  
Francois Lassailly ◽  
Katie Foster ◽  
Lourdes Lopez-Onieva ◽  
Erin Currie ◽  
Dominique Bonnet
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Comparative Analysis ◽  
Hematopoietic Stem Cells ◽  
Multimodal Imaging ◽  
Intravital Imaging ◽  
Functional Heterogeneity ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Functional Implications

Key Points Comparative analysis of epiphyses, diaphyses, and calvaria in terms of homeostatic HSC content, homing, and early reconstitution is described. Noninvasive intravital imaging of intact bones and assessment of BVF, BRA, and hypoxia are reported.

An animal model of adult T-cell leukemia: humanized mice with HTLV-1–specific immunity

Blood ◽  
2014 ◽  
Vol 123 (3) ◽  
pp. 346-355 ◽  
Author(s):  
Kenta Tezuka ◽  
Runze Xun ◽  
Mami Tei ◽  
Takaharu Ueno ◽  
Masakazu Tanaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Animal Model ◽  
Immune Responses ◽  
Humanized Mice ◽  
Cell Leukemia ◽  
Adaptive Immune Responses ◽  
Hematopoietic Stem ◽  
Adult T Cell Leukemia ◽  
Adaptive Immune ◽  
Key Points

Key Points Humanized mice, IBMI-huNOG, were generated by intra–bone marrow injection of human CD133+ hematopoietic stem cells. HTLV-1–infected IBMI-huNOG mice recapitulated distinct ATL-like symptoms as well as HTLV-1–specific adaptive immune responses.

scholarly journals Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up

Blood ◽  
2018 ◽  
Vol 131 (21) ◽  
pp. 2331-2334 ◽  
Author(s):  
Robert J. Kreitman ◽  
Martin S. Tallman ◽  
Tadeusz Robak ◽  
Steven Coutre ◽  
Wyndham H. Wilson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Phase 1 ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Key Points ◽  
Long Term Follow Up ◽  
Minimal Residual

Key Points Moxetumomab pasudotox eradicated HCL MRD in >50% of CRs, even by the most sensitive measure, bone marrow aspirate flow cytometry. Elimination of MRD was significantly associated with prolonged CR duration.

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