Marrow culture studies in adult acute leukemia at presentation and during remission

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 903-912
Author(s):  
PC Vincent ◽  
R Sutherland ◽  
M Bradley ◽  
D Lind ◽  
FW Gunz
Keyword(s):  
Proliferative Activity ◽  
Growth Patterns ◽  
Leukemic Cells ◽  
Type B ◽  
Culture Studies ◽  
Abnormal Growth ◽  
Pattern Type ◽  
Intermittent Chemotherapy ◽  
Acute Nonlymphoblastic Leukemia ◽  
Marked Proliferation

Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100–1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.

scholarly journals Marrow culture studies in adult acute leukemia at presentation and during remission

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 903-912 ◽  
Author(s):  
PC Vincent ◽  
R Sutherland ◽  
M Bradley ◽  
D Lind ◽  
FW Gunz
Keyword(s):  
Proliferative Activity ◽  
Growth Patterns ◽  
Leukemic Cells ◽  
Type B ◽  
Culture Studies ◽  
Abnormal Growth ◽  
Pattern Type ◽  
Intermittent Chemotherapy ◽  
Acute Nonlymphoblastic Leukemia ◽  
Marked Proliferation

Abstract Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100–1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.

scholarly journals Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 319-327 ◽  
Author(s):  
K Sawada ◽  
M Ieko ◽  
A Notoya ◽  
T Tarumi ◽  
K Koizumi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Clonal Growth ◽  
Growth Patterns ◽  
Leukemic Cells ◽  
Human Macrophage ◽  
Cluster Number ◽  
Gm Csf ◽  
Cd34 Cells

Abstract The clonal growth of progenitor cells from myelodysplastic syndromes (MDS) can be subdivided into four growth patterns: (1) normal, (2) no growth or low plating efficiency, (3) low colony and high cluster number, and (4) normal or high colony number with a large number of clusters. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cytokines in leukemic-type growth of MDS progenitor cells, marrow CD34+ cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). The purified CD34+ cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. The clonal growth of MDS CD34+ cells supported by a combination of all of the above cytokines was subdivided into the two patterns of leukemic or nonleukemic, and then the role of individual or combined cytokines in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. Evidence we obtained showed that SCF plays a central role in the leukemic-type growth of MDS CD34+ cells and that G-CSF, GM-CSF; and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34+ cells. SCF is present in either normal or MDS plasma at a level of nanograms per milliliter, and this physiologic concentration of SCF can stimulate progenitor cells. This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at least in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF.

A new diurnal gecko in the genus Gonatodes (Squamata: Sphaerodactylidae) from the foothills of the Serranía de San Lucas, Norosí-Colombia

Zootaxa ◽  
2020 ◽  
Vol 4877 (2) ◽  
pp. 345-360
Author(s):  
JUAN E. CARVAJAL-COGOLLO ◽  
JORGE A. EGUIS-AVENDAÑO ◽  
FABIO LEONARDO MEZA-JOYA
Keyword(s):  
New Species ◽  
Sea Level ◽  
Color Pattern ◽  
Type B ◽  
Molecular Analyses ◽  
Moderate Size ◽  
Pattern Type ◽  
Greenish Yellow ◽  
Riverine Forests ◽  
A New Species

We describe a new species of diurnal gecko, Gonatodes castanae sp. nov. from the foothills of the Serranía de San Lucas, municipality of Norosí, Department of Bolívar, Colombia. The new species differs from all species in the genus by the combination of the following characters: moderate size, subcaudal scale pattern type B (1’1’1’’), typically two rows of lateral scales on the digits, and aspects of color pattern in males (dorsum, flanks, limbs and tail with white ocelli on a black background) and females (dorsum, flanks, limbs and tail with brown to black reticulations and withe spots on a greenish-yellow background). The validity of the new species is also supported by molecular analyses. This species inhabits relicts of riverine forests at about 150 m above sea level (a.s.l.). Gonatodes castanae increases the number of known species in this genus to 34 and the species registered for Colombia to eight.

scholarly journals Pluripotent hemopoietic progenitors (CFU-GEMM) in polycythemia vera: analysis of erythropoietin requirement and proliferative activity

Blood ◽  
1981 ◽  
Vol 58 (6) ◽  
pp. 1224-1227 ◽  
Author(s):  
AA Fauser ◽  
HA Messner
Keyword(s):  
Polycythemia Vera ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Proliferative Activity ◽  
Growth Patterns ◽  
Short Term ◽  
Proliferative Rate ◽  
Normal Individuals ◽  
Short Term Exposure ◽  
Blood Specimens

Pluripotent hemopoietic progenitors (CFU-GEMM) give rise to multilineage hemopoietic colonies in culture. We have examined the erythropoietin requirements of CFU-GEMM-derived erythroid progeny in patients with polycythemia vera (PV) and studied their proliferative activity by short-term exposure to 3HTdR. Mixed colonies with erythroid components were observed in all bone marrow and peripheral blood samples from patients with PV that were cultured without addition of exogenous erythropoietin. This response is consistent with previously reported growth patterns for CFU-E and BFU-E. The frequency of mixed colonies increased regularly when erythropoietin was added to the cultures. Short-term exposure of peripheral blood specimens to 3HTdR prior to plating yielded a reduction of the plating efficiency by 20%- 70% when compared to cells that were not exposed to 3HTdR. The observation of cycling CFU-GEMM in PV contrasts with the usually quiescent behavior of CFU-GEMM in peripheral blood of normal individuals under steady-state conditions. These results support the view that the increased proliferative rate observed for CFU-GEMM may be responsible for the increased formation of blood cells in PV.

Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia.

1991 ◽  
Vol 9 (3) ◽  
pp. 400-405 ◽  
Author(s):  
E A Schriock ◽  
M J Schell ◽  
M Carter ◽  
O Hustu ◽  
J J Ochs
Keyword(s):  
Short Stature ◽  
Growth Retardation ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Onset ◽  
Cranial Irradiation ◽  
Growth Patterns ◽  
Research Attention ◽  
Abnormal Growth ◽  
Prophylactic Irradiation

Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention.

scholarly journals Deoxyribonucleoside triphosphate accumulation by leukemic cells

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 419-424 ◽  
Author(s):  
BS Mitchell ◽  
NL Edwards ◽  
CA Koller
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adenosine Deaminase ◽  
Lymphoblastic Leukemia ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Culture Cells ◽  
Acute Nonlymphoblastic Leukemia ◽  
Deoxyribonucleoside Triphosphate

Abstract The toxicity of the deoxyribonucleosides, 2′-deoxyadenosine, 2′- deoxyguanosine, and thymidine, for human T lymphoblasts is mediated by the accumulation of the corresponding deoxyribonucleoside triphosphate (dATP, dGTP, or dTTP, respectively). We have examined whether leukemic cells of non-T-cell origin are capable of accumulating deoxyribonucleotides in culture and whether this capability correlates with the activities of purine metabolizing enzymes in these cells. We have found that non-T, non-B acute lymphoblastic leukemia cells with low ecto-5′-nucleotidase and high adenosine deaminase activities increase their dATP pools by greater than tenfold when exposed to deoxyadenosine and an inhibitor of adenosine deaminase in culture. Cells from 2 of 9 patients with chronic lymphocytic leukemia and 4 of 11 patients with acute nonlymphoblastic leukemia achieved similar elevations in dATP, but there was no relationship between dATP accumulation and adenosine deaminase, purine nucleoside phosphorylase, or ecto-5′-nucleotidase activities. Treatment of four individuals with acute lymphoblastic leukemia with the adenosine deaminase inhibitor, 2′- deoxycoformycin, resulted in elevations in plasma deoxyadenosine concentrations and in increments in lymphoblast dATP levels that were similar to those measured in lymphoblasts cultured with deoxyadenosine and deoxycoformycin prior to treatment. In vitro incubations of leukemic cells with deoxyribonucleosides may provide a rational basis for the use of these compounds as chemotherapeutic agents.

Deregulated Expression of a Novel Oncogene, Ahi-1, in Murine Hematopoietic Cells Confers a Proliferative Advantage In Vitro and Leukemogenic Activity In Vivo and Enhances the Effects of BCR-ABL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 388-388
Author(s):  
Leon Zhou ◽  
Ashley Ringrose ◽  
Ann E.-J. Lin ◽  
Xiaoyan Jiang
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Western Blot ◽  
Proliferative Activity ◽  
Integration Site ◽  
Hematopoietic Cells ◽  
Leukemic Cells ◽  
Biological Behavior

Abstract Ahi-1 (Abelson helper integration site-1) is a novel gene that we recently identified based on its common activation in v-abl or myc-induced murine leukemias and lymphomas. It encodes a unique protein with known signaling features, including SH3 and WD40-repeat domains, but its function is largely unknown. We have recently demonstrated that Ahi-1/AHI-1 transcript levels are normally down-regulated during both early murine and human hematopoietic cell differentiation and are highly increased in human leukemic cells, particularly in highly enriched populations of primitive BCR-ABL+ leukemic stem cells (lin−CD34+CD38−) in patients with chronic myeloid leukemia (CML). To investigate the potential cooperative activity of Ahi-1 in BCR-ABL-mediated signal transduction and leukemogenesis, we transduced IL-3-dependent BaF3 cells with MSCV-Ahi-1-IRES-YFP and/or MSCV-BCR-ABL-IRES-GFP retroviruses and compared the biological behavior of these cells in vitro and in vivo. All Ahi-1-transduced clonal cell lines showed increased proliferative activity and reduced apoptosis in the absence of IL-3, compared to parental BaF3 cells or control GFP-transduced cells. Interestingly, overexpression of both Ahi-1 and BCR-ABL caused more enhanced perturbations when compared to cells transduced with either Ahi-1 or BCR-ABL alone. Strikingly, intravenous injection of NOD/SCID-β2microglobulin−/−mice with BaF3 cells induced to overexpress Ahi-1 alone induces a lethal leukemia within 70 days. These leukemogenic activities were further increased by introduction of co-transduced Ahi-1 and BCR-ABL cells, producing a shorter latency of 30 days. A disease latency of 40 days was revealed by introduction of BCR-ABL-transduced cells alone. Western blot analysis showed that both protein expression and the tyrosine kinase activity of p210BCR-ABL were highly increased in cells co-transduced with Ahi-1 and BCR-ABL compared to BaF3 cells transduced with BCR-ABL alone. Similarly, we also observed higher levels of Ahi-1 protein expression in the same dually transduced cells (Ahi-1+BCR-ABL+) than in those transduced with Ahi-1 alone. We further demonstrated a similarly perturbed proliferative activity, growth factor independence and colony-forming cell (CFC) output in long-term culture initiated cell (LTC-IC) assays of 5-fluorouracil (5-FU)-treated primitive murine BM cells (Lin−Sca1+ cells) transduced with Ahi-1 and BCR-ABL, either alone or in combination. To investigate directly the cooperating oncogenic role of AHI-1 in BCR-ABL-mediated malignant transformation of CML cells, knockdown of AHI-1 expression in K562 cells, a cell line that was derived from a patient with CML and that is characterized by highly increased expression of AHI-1, was performed using retroviral-mediated RNA interference. Retroviral-mediated suppression specifically inhibited endogenous AHI-1 expression in transduced cells by 70% as evaluated by Q-RT-PCR and Western blot analyses. It further caused a significant reduction in their growth factor independence in semi-solid cultures (up to 5-fold) and in single cell cultures (2-fold) by comparison to cells transduced with a control vector. Taken together, these findings provide strong evidence of the transforming potential of Ahi-1/AHI-1 in primitive hematopoietic cells. This effect is additive with those of BCR-ABL, suggesting that AHI-1 and BCR-ABL can play a cooperate role in the development of BCR-ABL-associated diseases like CML.

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