scholarly journals Karyotypically distinct subpopulations in acute leukemia with specific growth requirements

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 641-645 ◽  
Author(s):  
B Lowenberg ◽  
A Hagemeijer ◽  
K Swart
Keyword(s):  
Leukemic Cell ◽  
Clinical History ◽  
Malignant Cell ◽  
Biological Properties ◽  
Myeloid Differentiation ◽  
Tumor Stem Cells ◽  
Growth Requirements ◽  
Acute Monoblastic Leukemia ◽  
History Of

Bone marrow and blood cells of a patient with acute monoblastic leukemia with subclones marked with specific karyotypic abnormalities were investigated. In order to more precisely evaluate the proliferative abilities of these populations, leukemic cell enriched fractions were prepared and incubated in two colony assays. Colony forming cells of the disparate clones had growth advantages in different systems which shows that their proliferation depended on the presence of selective stimulatory factors in culture. In one assay, at diagnosis, colonies from the minor clone were demonstrated exclusively. It is suggested that the assays measured distinct cellular stages of myeloid differentiation and the findings indicate that prior to diagnosis the neoplasm had evolved into subsets with progressive dedifferentiation. Differences of growth in vitro correlated with the different roles of these clones in the clinical history of the disease. Approaches based on differential cloning of tumor stem cells as in this example, may be useful for discriminating biological properties of heterogeneous subpopulations within neoplasms, and may facilitate the cytogenetic recognition of minimal clones among composite malignant cell specimens.

Karyotypically distinct subpopulations in acute leukemia with specific growth requirements

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 641-645 ◽  
Author(s):  
B Lowenberg ◽  
A Hagemeijer ◽  
K Swart
Keyword(s):  
Leukemic Cell ◽  
Clinical History ◽  
Malignant Cell ◽  
Biological Properties ◽  
Myeloid Differentiation ◽  
Tumor Stem Cells ◽  
Growth Requirements ◽  
Acute Monoblastic Leukemia ◽  
History Of

Abstract Bone marrow and blood cells of a patient with acute monoblastic leukemia with subclones marked with specific karyotypic abnormalities were investigated. In order to more precisely evaluate the proliferative abilities of these populations, leukemic cell enriched fractions were prepared and incubated in two colony assays. Colony forming cells of the disparate clones had growth advantages in different systems which shows that their proliferation depended on the presence of selective stimulatory factors in culture. In one assay, at diagnosis, colonies from the minor clone were demonstrated exclusively. It is suggested that the assays measured distinct cellular stages of myeloid differentiation and the findings indicate that prior to diagnosis the neoplasm had evolved into subsets with progressive dedifferentiation. Differences of growth in vitro correlated with the different roles of these clones in the clinical history of the disease. Approaches based on differential cloning of tumor stem cells as in this example, may be useful for discriminating biological properties of heterogeneous subpopulations within neoplasms, and may facilitate the cytogenetic recognition of minimal clones among composite malignant cell specimens.

Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo [see comments]

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1965-1971 ◽  
Author(s):  
R Landolfi ◽  
G Ciabattoni ◽  
P Patrignani ◽  
MA Castellana ◽  
E Pogliani ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Clinical History ◽  
Current Treatment ◽  
Lipoxygenase Pathway ◽  
Binding Characteristics ◽  
History Of ◽  
Thrombotic Complications ◽  
Excretion Rates

Abstract Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

In Vitro Induction of Differentiation in HL-60 Leukemic Cell Line by Clerodendron Fragrans

1988 ◽  
Vol 16 (03n04) ◽  
pp. 139-144 ◽  
Author(s):  
Po-min Chen ◽  
Lin-lin Yung ◽  
Kuo-I Hsiao ◽  
Chien-ming Chen ◽  
Hsin-mei Yeh ◽  
...  
Keyword(s):  
Cell Line ◽  
Chinese Herb ◽  
Leukemic Cell ◽  
Myeloid Differentiation ◽  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Therapeutic Value ◽  
Induction Of Differentiation ◽  
In Vitro Induction

The promyelocytic cell line HL-60 could be induced to differentiate into morphologically and functionally mature monocytoid cells (up to 20%) following exposure to the Chinese herb Clerodendron Fragrans (1 mg/ml). This effect was time dependent and appeared to work synergistically with interferon-r in this promotion of differentiation. Our study suggests that Clerodendron Fragrans has potential therapeutic value for the treatment of certain acute myelocytic leukemia putatively caused by a block in the myeloid differentiation process.

scholarly journals Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo [see comments]

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1965-1971 ◽  
Author(s):  
R Landolfi ◽  
G Ciabattoni ◽  
P Patrignani ◽  
MA Castellana ◽  
E Pogliani ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Clinical History ◽  
Current Treatment ◽  
Lipoxygenase Pathway ◽  
Binding Characteristics ◽  
History Of ◽  
Thrombotic Complications ◽  
Excretion Rates

Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

scholarly journals Thymodepressin—Unforeseen Immunosuppressor

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6550
Author(s):  
Vladislav I. Deigin ◽  
Julia E. Vinogradova ◽  
Dmitry L Vinogradov ◽  
Marina S. Krasilshchikova ◽  
Vadim T. Ivanov
Keyword(s):  
Experimental Evidence ◽  
Synthetic Peptide ◽  
Biomedical Applications ◽  
Biological Properties ◽  
Peptide Drug ◽  
Wide Range ◽  
History Of ◽  
Available Information

The paper summarizes the available information concerning the biological properties and biomedical applications of Thymodepressin. This synthetic peptide drug displays pronounced immunoinhibitory activity across a wide range of conditions in vitro and in vivo. The history of its unforeseen discovery is briefly reviewed, and the current as well as potential expansion areas of medicinal practice are outlined. Additional experimental evidence is obtained, demonstrating several potential advantages of Thymodepressin over another actively used immunosuppressor drug, cyclosporin A.

scholarly journals Retention of dopamine 2 receptor mRNA and absence of the protein in craniospinal and extracranial metastasis of a malignant prolactinoma: a case report

2002 ◽  
pp. 81-88 ◽  
Author(s):  
J Winkelmann ◽  
U Pagotto ◽  
M Theodoropoulou ◽  
K Tatsch ◽  
W Saeger ◽  
...  
Keyword(s):  
Single Case ◽  
Clinical History ◽  
Extracranial Metastasis ◽  
Invasion And Metastasis ◽  
History Of ◽  
Dopamine 2 Receptor ◽  
Immunohistochemical Techniques

OBJECTIVES: The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists. DESIGN: Together with an extensive description of the clinical history of this case, a combination of in vitro and in vivo techniques was performed to provide the basis of the dopamine resistance developed in the course of the disease. METHOD: A comparison of the D2R was performed in specimens obtained at presentation of the disease compared with autoptic specimens derived from local invasion and metastasis using in situ hybridization and immunohistochemical techniques. RESULTS: Intact D2R mRNA was found in the primitive tumor and metastatic tissues, whereas protein for the same receptor was present only in the tissues derived from neurosurgical operations and not in the metastases obtained post-mortem. CONCLUSION: This is the first report of the absence of D2R protein despite the retention of the transcript in an advanced stage of a malignant prolactinoma. The findings of this single case suggest the hypothesis that postranscriptional mechanisms may contribute to the development of dopamine resistance in prolactinomas.

Dexamethasone does not prevent malignant cell reintroduction in leukemia patients undergoing ovarian transplant: risk assessment of leukemic cell transmission by a xenograft model

2019 ◽  
Vol 34 (8) ◽  
pp. 1485-1493
Author(s):  
César Díaz-García ◽  
Sonia Herraiz ◽  
Esperanza Such ◽  
María del Mar Andrés ◽  
Eva Villamón ◽  
...  
Keyword(s):  
Ovarian Tissue ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Malignant Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Malignant Cells ◽  
Immunodeficient Mice ◽  
Ovarian Cortex

Abstract STUDY QUESTION Does dexamethasone (DXM) incubation avoid the reintroduction of leukemic malignant cells after ovarian tissue retransplantation in vivo? SUMMARY ANSWER DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. WHAT IS KNOWN ALREADY Retransplantation of cryopreserved ovarian cortex from patients diagnosed with acute lymphoblastic leukemia (ALL) involves a risk of reintroducing malignant cells. DXM treatment is effective at inducing leukemic cell death in vitro. STUDY DESIGN, SIZE, DURATION This was an experimental study where ovarian cortex fragments from patients with ALL were randomly allocated to incubation with or without DXM (n = 11/group) and grafted to 22 immunodeficient mice for 6 months. In a parallel experiment, 22 immunodeficient mice were injected i.p. with varying amounts of RCH-ACV ALL cells (human leukemia cell line) and maintained for 4 months. PARTICIPANTS/MATERIALS, SETTING, METHODS Cryopreserved ovarian fragments from patients with ALL were exposed in vitro to 0.4 μM DXM or basal media (control) prior to xenograft into ovariectomized severe combined immunodeficiency (SCID) mice (experiment 1). After 6 months of monitoring, leukemia cell contamination was assessed in ovarian grafts and mouse organs by histology, PCR (presence of mouse mtDNA and absence of p53 were together considered a negative result for the presence of human cells) and detection of immunoglobulin monoclonality and specific ALL markers if present in the patient. In experiment 2, a series of 22 immunodeficient female mice was injected with specific doses of the leukemia cell line RCH-ACV (103 − 5 × 106, n = 4/group) to assess the engraftment competence of the SCID model. MAIN RESULTS AND THE ROLE OF CHANCE ALL metastatic cells were detected, by PCR, in five DXM-treated and one control human ovarian tissue graft as well as in a control mouse liver, although malignant cell infiltration was not detected by histology in any sample after 6 months. In total, minimal residual disease was present in three DXM-treated and three control mice. RCH-ACV cells were detected in liver and spleen samples after the injection of as little as 103 cells, although only animals receiving 5 × 106 cells developed clinical signs of disease and metastases. LIMITATIONS, REASONS FOR CAUTION This is an experimental study where the malignant potential of leukemic cells contained in human ovarian tissues has been assessed in immunodeficient mice. WIDER IMPLICATIONS OF THE FINDINGS These results indicate that DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. Therefore, caution should be taken in retransplanting ovarian tissue from patients with leukemia until safer systems are developed, as leukemic cells present in ovarian grafts were able to survive, proliferate and migrate after cryopreservation and xenograft. STUDY FUNDING/COMPETING INTEREST(S) Funded by the Regional Valencian Ministry of Education (PROMETEO/2018/137) and by the Spanish Ministry of Economy and Competitiveness (PI16/FIS PI16/01664 and PTQ-16-08222 for S.H. participation). There are no competing interests.

scholarly journals Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Almudena Sacristan-Reviriego ◽  
Hoang Mai Le ◽  
Michalis Georgiou ◽  
Isabelle Meunier ◽  
Beatrice Bocquet ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Disease Onset ◽  
Clinical History ◽  
Hypomorphic Allele ◽  
Functional Assays ◽  
Rich Domain ◽  
History Of ◽  
Functional Analyses ◽  
Retinal Cgmp Phosphodiesterase

Abstract Disease-causing sequence variants in the highly polymorphic AIPL1 gene are associated with a broad spectrum of inherited retinal diseases ranging from severe autosomal recessive Leber congenital amaurosis to later onset retinitis pigmentosa. AIPL1 is a photoreceptor-specific co-chaperone that interacts with HSP90 to facilitate the stable assembly of retinal cGMP phosphodiesterase, PDE6. In this report, we establish unequivocal correlations between patient clinical phenotypes and in vitro functional assays of uncharacterized AIPL1 variants. We confirm that missense and nonsense variants in the FKBP-like and tetratricopeptide repeat domains of AIPL1 lead to the loss of both HSP90 interaction and PDE6 activity, confirming these variants cause LCA. In contrast, we report the association of p.G122R with milder forms of retinal degeneration, and show that while p.G122R had no effect on HSP90 binding, the modulation of PDE6 cGMP levels was impaired. The clinical history of these patients together with our functional assays suggest that the p.G122R variant is a rare hypomorphic allele with a later disease onset, amenable to therapeutic intervention. Finally, we report the primate-specific proline-rich domain to be dispensable for both HSP90 interaction and PDE6 activity. We conclude that variants investigated in this domain do not cause disease, with the exception of p.A352_P355del associated with autosomal dominant cone-rod dystrophy.

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