scholarly journals Prediction of response to chemotherapy in acute myelocytic leukemia

Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 361-367 ◽  
Author(s):  
HD Preisler
Keyword(s):  
Cytosine Arabinoside ◽  
Chemotherapeutic Agents ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
Metabolic Resistance ◽  
Clear Cut ◽  
Myelocytic Leukemia ◽  
Response To Chemotherapy

Abstract Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between kinetic and metabolic resistance to cytosine arabinoside. The sensitivity of the colony- forming cells to the two chemotherapeutic agents did not correlate with each other, indicating that sensitivity to each was independently determined. The relationship between in vitro sensitivity to daunorubicin and cytosine arabinoside and response to 25 courses of in vivo therapy with these two agents administered to 21 patients was determined. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response with patients whose leukemic cells were sensitive to both agents entering complete remission, whereas patients whose leukemic cells were insensitive to one or both drugs in vitro failed to enter remission.

scholarly journals Prediction of response to chemotherapy in acute myelocytic leukemia

Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 361-367 ◽  
Author(s):  
HD Preisler
Keyword(s):  
Cytosine Arabinoside ◽  
Chemotherapeutic Agents ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
Metabolic Resistance ◽  
Clear Cut ◽  
Myelocytic Leukemia ◽  
Response To Chemotherapy

Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between kinetic and metabolic resistance to cytosine arabinoside. The sensitivity of the colony- forming cells to the two chemotherapeutic agents did not correlate with each other, indicating that sensitivity to each was independently determined. The relationship between in vitro sensitivity to daunorubicin and cytosine arabinoside and response to 25 courses of in vivo therapy with these two agents administered to 21 patients was determined. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response with patients whose leukemic cells were sensitive to both agents entering complete remission, whereas patients whose leukemic cells were insensitive to one or both drugs in vitro failed to enter remission.

In vivo and in vitro activity of neutrophil alkaline phosphatase in acute myelocytic leukemia with 8;21 translocation

Blood ◽  
1981 ◽  
Vol 58 (6) ◽  
pp. 1213-1217
Author(s):  
N Kamada ◽  
H Dohy ◽  
K Okada ◽  
N Oguma ◽  
A Kuramoto ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Genetic Alterations ◽  
Leukemic Cells ◽  
Characteristic Subgroup ◽  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Fab Classification ◽  
Neutrophil Alkaline Phosphatase

Cytogenetic studies were made on 160 patients with acute nonlymphocytic leukemia (ANLL) between 1963 and 1979, of whom 115 had acute myelocytic leukemia with 67 patients showing aneuploidy (58.3%). Among these, 24 patients were found to have similar chromosome alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies on at least 7 of these patients confirmed the presence of a translocation between these two chromosomes. Of 160 ANLL patients, 142 were scored for neutrophil alkaline phosphatase (neutrophil AP) at the time of diagnosis. Fifty-nine patients showed a low neutrophil AP score, 42 a normal value, and 41 a high value. All patients with 8;21 (or C/G) translocation had a low neutrophil AP score and leukemic cells with maturation (M2 of FAB classification) in the bone marrow. In vitro liquid culture for 2 wk of 8;21 translocated leukemic cells revealed no increase of neutrophil AP activity nor increase of mature granulocytes, whereas 9;22 translocated chronic myelocytic leukemia cells with a low neutrophil AP score did so. Neutrophil AP score at the time of diagnosis in acute myelocytic leukemia is very useful for detecting 8;21 translocation AML and for studying the pathophysiology and genetic alterations of the characteristic subgroup of AML with 8′21 translocation.

scholarly journals In vivo and in vitro activity of neutrophil alkaline phosphatase in acute myelocytic leukemia with 8;21 translocation

Blood ◽  
1981 ◽  
Vol 58 (6) ◽  
pp. 1213-1217 ◽  
Author(s):  
N Kamada ◽  
H Dohy ◽  
K Okada ◽  
N Oguma ◽  
A Kuramoto ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Genetic Alterations ◽  
Leukemic Cells ◽  
Characteristic Subgroup ◽  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Fab Classification ◽  
Neutrophil Alkaline Phosphatase

Abstract Cytogenetic studies were made on 160 patients with acute nonlymphocytic leukemia (ANLL) between 1963 and 1979, of whom 115 had acute myelocytic leukemia with 67 patients showing aneuploidy (58.3%). Among these, 24 patients were found to have similar chromosome alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies on at least 7 of these patients confirmed the presence of a translocation between these two chromosomes. Of 160 ANLL patients, 142 were scored for neutrophil alkaline phosphatase (neutrophil AP) at the time of diagnosis. Fifty-nine patients showed a low neutrophil AP score, 42 a normal value, and 41 a high value. All patients with 8;21 (or C/G) translocation had a low neutrophil AP score and leukemic cells with maturation (M2 of FAB classification) in the bone marrow. In vitro liquid culture for 2 wk of 8;21 translocated leukemic cells revealed no increase of neutrophil AP activity nor increase of mature granulocytes, whereas 9;22 translocated chronic myelocytic leukemia cells with a low neutrophil AP score did so. Neutrophil AP score at the time of diagnosis in acute myelocytic leukemia is very useful for detecting 8;21 translocation AML and for studying the pathophysiology and genetic alterations of the characteristic subgroup of AML with 8′21 translocation.

scholarly journals Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1329-1332 ◽  
Author(s):  
DC Kaufman ◽  
MR Baer ◽  
XZ Gao ◽  
ZQ Wang ◽  
HD Preisler
Keyword(s):  
T Cell ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Myelocytic Leukemia ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.

scholarly journals A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaojin Li ◽  
Hua Guo ◽  
Yanlian Yang ◽  
Jie Meng ◽  
Jian Liu ◽  
...  
Keyword(s):  
Acute Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Peptide Targeting

scholarly journals Decitabine Augments Chemotherapy-Induced PD-L1 Upregulation for PD-L1 Blockade in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 462 ◽  
Author(s):  
Kevin Chih-Yang Huang ◽  
Shu-Fen Chiang ◽  
William Tzu-Liang Chen ◽  
Tsung-Wei Chen ◽  
Ching-Han Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Efficacy ◽  
Dna Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Dna Hypomethylation ◽  
Chemotherapeutic Regimen ◽  
Response To Chemotherapy ◽  
Clinical Benefits

Programmed cell death-1 (PD-1) has demonstrated impressive clinical outcomes in several malignancies, but its therapeutic efficacy in the majority of colorectal cancers is still low. Therefore, methods to improve its therapeutic efficacy in colorectal cancer (CRC) patients need further investigation. Here, we demonstrate that immunogenic chemotherapeutic agents trigger the induction of tumor PD-L1 expression in vitro and in vivo, a fact which was validated in metastatic CRC patients who received preoperatively neoadjuvant chemotherapy (neoCT) treatment, suggesting that tumor PD-L1 upregulation by chemotherapeutic regimen is more feasible via PD-1/PD-L1 immunotherapy. However, we found that the epigenetic control of tumor PD-L1 via DNA methyltransferase 1 (DNMT1) significantly influenced the response to chemotherapy. We demonstrate that decitabine (DAC) induces DNA hypomethylation, which not only directly enhances tumor PD-L1 expression but also increases the expression of immune-related genes and intratumoral T cell infiltration in vitro and in vivo. DAC was found to profoundly enhance the therapeutic efficacy of PD-L1 immunotherapy to inhibit tumor growth and prolong survival in vivo. Therefore, it can be seen that DAC remodels the tumor microenvironment to improve the effect of PD-L1 immunotherapy by directly triggering tumor PD-L1 expression and eliciting stronger anti-cancer immune responses, providing potential clinical benefits to CRC patients in the future.

scholarly journals Expression of embryonic globins by erythroid cells in juvenile chronic myelocytic leukemia

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2569-2576 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
NP Anagnou ◽  
D Chui ◽  
L Dow ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Fetal Hemoglobin ◽  
Colony Growth ◽  
Leukemic Cells ◽  
Chronic Myelocytic Leukemia ◽  
Erythroid Cells ◽  
Myelocytic Leukemia ◽  
Synthetic Profile

Abstract Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as reported previously. Furthermore, in contrast to previous reports, we found significant erythroid colony growth in most of our cases (average: 1,182 burst- forming unit-erythroid [BFUe] per 10(5) plated cells, range: 40 to 6,927). This growth was by and large erythropoietin-dependent and was not greatly influenced by other added cytokines. By several criteria all erythroid colony growth detected in vitro was derived from JCML progenitors. The globin synthetic profile of JCML erythroid cells showed high levels of fetal hemoglobin both in vivo and in vitro (gamma/gamma + beta: 53% to 94% in reticulocytes, 62% to 98% in BFUe- derived cells). In addition (in seven cases studied) we detected embryonic globins (epsilon and zeta) at the protein and messenger RNA level, a novel finding for primary leukemic cells. We speculate that the transformed erythroid cells in JCML harbor a trans environment supporting expression of developmentally earlier genes (fetal, embryonic). However, in contrast to other acute or subacute leukemias, JCML erythroid cells also have the ability to reach full maturation to the red cell level, thus allowing detection of this primitive program in vivo.

Prevention of leptin binding to its receptor suppresses rat leukemic cell growth by inhibiting angiogenesis

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4123-4128 ◽  
Author(s):  
Per Ole Iversen ◽  
Christian Andre Drevon ◽  
Janne Elin Reseland
Keyword(s):  
Bone Marrow ◽  
Cell Growth ◽  
Leptin Receptor ◽  
Mononuclear Cells ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
In Vitro Proliferation

Leptin promotes the growth and viability of hematopoietic cells, and it also stimulates microvessel formation, indicating a role for leptin in angiogenesis. Acute myelocytic leukemia (AML) remains a disease with poor prognosis. Similar to solid tumors, it probably requires angiogenesis to ensure adequate supplies of nutrients. We studied rats with transplanted AML to test if a neutralizing anti–leptin receptor monoclonal antibody (mAb) (anti–OB-R) could inhibit leukemogenesis. At 4 weeks after transplantation, the bone marrow contained about 80% leukemic cells as assayed with a specific mAb and flow cytometry. Microscopic examination of bone marrow sections stained with an anti–von Willebrand mAb revealed a marked increase in microvessel density in the leukemic rats compared with controls. Treatment with anti–OB-R for 3 weeks more than halved the content of bone marrow leukemic cells with a concomitant, substantial decrease in angiogenesis. A parallel experiment using an irrelevant anticasein mAb showed no effect on either leukemic cell growth or angiogenesis. We could not detect surface expression of the leptin receptor on the leukemic cells, but on mononuclear cells from healthy rats. The anti–OB-R did not affect in vitro proliferation of leukemic cells whereas proliferation of the mononuclear cells was markedly impaired. The anti–OB-R had no effect on either leukemic cell growth or angiogenesis in leukemic fa/fa rats with a mutated leptin receptor. We conclude that leptin stimulates leukemic cell growth in vivo by promoting angiogenesis. Inhibition of binding of leptin to its receptor might be a new adjunct therapy in AML.

scholarly journals Expression of embryonic globins by erythroid cells in juvenile chronic myelocytic leukemia

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2569-2576 ◽  
Author(s):  
T Papayannopoulou ◽  
B Nakamoto ◽  
NP Anagnou ◽  
D Chui ◽  
L Dow ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Fetal Hemoglobin ◽  
Colony Growth ◽  
Leukemic Cells ◽  
Chronic Myelocytic Leukemia ◽  
Erythroid Cells ◽  
Myelocytic Leukemia ◽  
Synthetic Profile

Juvenile chronic myelocytic leukemia (JCML) is a rare hematopoietic neoplasia of early childhood with distinct hematologic and biochemical features. We studied the biologic properties and the globin synthetic profiles of JCML erythroid cells both in vivo and in vitro from a total of 24 patients. In these cases we observed the exuberant colony-forming unit-macrophage (CFU-M) colony growth, as reported previously. Furthermore, in contrast to previous reports, we found significant erythroid colony growth in most of our cases (average: 1,182 burst- forming unit-erythroid [BFUe] per 10(5) plated cells, range: 40 to 6,927). This growth was by and large erythropoietin-dependent and was not greatly influenced by other added cytokines. By several criteria all erythroid colony growth detected in vitro was derived from JCML progenitors. The globin synthetic profile of JCML erythroid cells showed high levels of fetal hemoglobin both in vivo and in vitro (gamma/gamma + beta: 53% to 94% in reticulocytes, 62% to 98% in BFUe- derived cells). In addition (in seven cases studied) we detected embryonic globins (epsilon and zeta) at the protein and messenger RNA level, a novel finding for primary leukemic cells. We speculate that the transformed erythroid cells in JCML harbor a trans environment supporting expression of developmentally earlier genes (fetal, embryonic). However, in contrast to other acute or subacute leukemias, JCML erythroid cells also have the ability to reach full maturation to the red cell level, thus allowing detection of this primitive program in vivo.

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