Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ara-C sensitivity test and suicide tests of L-CFU using [3H] deoxycytidine (dCyd) and [3H] thymidine (TdR) were performed in patients with acute nonlymphocytic leukemia (ANLL) and with chronic myeloid leukemia in blastic crisis (CML-BC). We found a correlation between ara-C sensitivity and the [3H] dCyd suicide test of L-CFU (p less than 0.001); and between ara-C sensitivity and the [3H] TdR suicide test (p less than 0.05). These results suggest that the [3H] dCyd suicide test reflects the degree of activity of ara-C metabolism in L-CFUs.
 ...
PMID:[Relationship between Ara-C sensitivity of leukemic-colony forming units (L-CFU) and [3H] deoxycytidine suicide test of L-CFU]. 261 40

The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 +/- 9% (SEM) of control at 0.3 microM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 +/- 12% CML chronic phase, 58 +/- 26% MPD at 3.0 microM RA). At 0.3 microM and 1.0 microM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p less than 0.02 and p less than 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progenitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 +/- 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.
 ...
PMID:Inhibition by retinoic acid of myeloid progenitors in chronic myeloid leukemia and myeloproliferative disease: increased sensitivity in blastic phase of chronic myeloid leukemia. 316 96

Conditioned media from the human myeloid leukemic cell line ML-2 contain a factor that inhibits the entry of normal CFU-GM into S phase of mitotic cycle as measured by the 3H-TdR suicide technique. This factor was detected in conditioned media prepared by incubating 5 X 10(6) ML-2 cells/ml or 1 X 10(6) ML-2 cells/ml in serum-free RPMI for 5 or 24 hours respectively, and was isolated by ultrafiltration through an XM 300 Diaflo membrane followed by chromatography on Sepharose 6 B. Ferritin, prepared from human placenta, had the same inhibitory effect on CFU-GM. Antibodies against human placental ferritin completely inactivated the inhibitory effect of both human placental ferritin and the factor released from ML-2 cells. The inhibitory activity produced by the cell-line ML-2 was considered as LIA (leukemia cell-derived inhibitory activity) earlier found in HL-60 cell line and AML and CML cells.
 ...
PMID:Identification of leukemia cell-derived inhibitory activity (LIA) in conditioned media from human myeloid leukemic cell line ML-2. 348 46

In serum from chronic myelogenous leukemia (CML) patients an activity has been demonstrated, which recruits more CFU-GM (cells committed to granulocyte-macrophage lineage) from normal human bone marrow into clonal proliferation as shown by standard agar colony forming assay, in the presence of supramaximal levels of colony stimulating activity. All sera from CML patients at diagnosis (before therapy) were tested and found to be significantly (P less than 0.001) positive for the recruitment activity. This observation led us to believe that younger or more pluripotent CFU-GM which were hitherto non-responsive to colony stimulating activity become responsive in the presence of CML sera. We investigated whether more pluripotent stem cells (CFUs) are stimulated to proliferate in the chronic phase of CML than at diagnosis (before therapy). An activity was detected which recruits more spleen colony forming cells (CFUs) from normal Swiss mouse bone marrow into the cell cycle as shown by a significant increase (P less than 0.001) in the thymidine suicide index. However both these activities were either lowered or undetectable in normal (blood groups AB) serum. These results indicate that CML sera may contain enhanced levels of early growth factors which stimulate proliferation of pluripotent stem cells resulting in an increased CFU-GM pool in CML. It is suggested that this activity may be responsible for the myeloid hyperplasia associated with CML in the chronic phase.
 ...
PMID:Evidence for the presence in sera from chronic myelogenous leukemia patients of an activity that enhances the number of normal bone marrow-derived granulocyte/monocyte committed stem cell colonies. 350 Nov 8

Twenty-three patients with chronic-phase CML have been treated with intermittent courses of busulfan to determine if the duration of unmaintained remission becomes progressively shorter with successive courses of therapy and to determine whether there was a relationship between cluster and colony formation, suicide index of CFUc, labeling index, percentage of cells in S-phase (as determined by cytofluorographic DNA histogram analysis), in vitro sensitivity of the CFUc to busulfan, and response to busulfan therapy. Serial studies in individual patients and the group as a whole revealed no relationship between changes in the cellular parameters described above and response to busulfan. The white blood cell (WBC) doubling time with serial courses of busulfan in individual patients did not always progressively decrease as has been previously reported. In vitro studies of CFUc in chronic-phase CML appear to be of no value in predicting response to busulfan.
 ...
PMID:Lack of relationship between in vitro cell measurements and response to busulfan in chronic myelocytic leukemia. 385 99

The effects of three S-phase-specific agents, [3H]thymidine, hydroxyurea, and 1-beta-D-arabinofuranosylcytosine, on granulocyte-macrophage colony-forming units (CFU-C) and erythroid progenitor cells (erythroid burst-forming units) (BFU-E) from the bone marrow or peripheral blood obtained from 23 normal individuals and 12 patients with chronic myelogenous leukemia were investigated. CFU-C, regardless of their source, showed comparable degrees of sensitivity to each of the S-phase-specific agents, with perhaps a slightly greater level of sensitivity to [3H]thymidine. In contrast, the sensitivities of chronic myelogenous leukemia and normal marrow BFU-E to the 3 agents were quite different, with essentially all BFU-E being killed by [3H]thymidine, 50 to 70% being killed by 1-beta-D-arabinofuranosylcytosine, and only 15 to 20% being killed by hydroxyurea. BFU-E present in normal peripheral blood were insensitive to [3H]thymidine or hydroxyurea but were sensitive to 1-beta-D-arabinofuranosylcytosine. These studies demonstrated similarities between the CFU-C and BFU-E of CML patients and the CFU-C and BFU-E present in normal bone marrow. On the other hand, the sensitivities of normal peripheral blood progenitor cells to "S-phase-specific" agents differed from that of CML progenitor cells or the progenitor cells present in normal bone marrow. Additionally, these studies have demonstrated the limitations inherent in suicide techniques as methods for estimating the cell cycle characteristics of clonogenic cells.
 ...
PMID:Effects of S-phase-specific agents on granulocyte-macrophage and erythroid progenitor cells obtained from normal individuals and from patients with chronic myelogenous leukemia. 657 19

Serial clonogenicity studies employing an agar CFUc culture assay are being performed on cells from CML patients to determine if clonal growth, 3HTdR suicide indices (SI) and in vitro busulfan sensitivity are of prognostic significance in predicting blastic transformation. Initial studies performed on specimens obtained from 20 chronic phase patients were directed at determining whether blood and marrow cells differed in growth pattern, SI, and busulfan sensitivity and whether the cells giving rise to clusters differed from those forming colonies. In comparing marrow to blood cells, there was a correlation between the two with respect to the number of colonies produced and the sensitivity of the clonogenic cells to busulfan. By contrast the SI of blood and marrow clonogenic cells were not correlated. In both blood and marrow, colony forming cells had a higher SI and were more sensitive to busulfan than were cluster forming cells.
 ...
PMID:In vitro drug sensitivity studies of CFUc in chronic myelocytic leukemia: I. Suicide indices and busulfan sensitivity determinations during the chronic phase. 657 10

Attempts to eliminate Philadelphia chromosome-positive cells during the treatment of chronic-phase chronic myelocytic leukemia (CML) have been largely unsuccessful, probably due to the lack of specificity of drugs which have been used. In an attempt to develop more specific therapy for CML, an assay for colony-forming units in culture was used to test for differences between CML blood and normal marrow progenitor cells. The following drugs, which have activity in acute nonlymphocytic leukemia, were tested over a range of concentrations achievable in vivo: Adriamycin; 1-beta-D-arabinofuranosylcytosine; aclacinomycin; m(4-acridinylamino)-3-methoxyphenyl methansulfamide; methylglyoxalbis(guanylhydrazone), and 5-azacytidine. [3H]Thymidine suicide indices were also determined. Normal marrow colony-forming units in culture tended to be more sensitive to all the drugs which were tested, although not of statistical significance. There was no difference in the suicide index between CML and normal colony-forming units in culture. It is concluded that the drugs which were tested are not likely to selectively kill CML progenitor cells while permitting normal hematopoietic elements to survive.
 ...
PMID:In vitro drug sensitivity studies of colony-forming units in culture in chronic myelocytic leukemia: lack of specificity between chronic-phase patients and normal donors. 658 67

In order to study the pathogenesis of juvenile-type chronic myelocytic leukemia (CML), we examined the colony-forming capacity and colony composition in the bone marrow (BM) and peripheral blood (PB) of three children with juvenile-type CML. Large numbers of granulocytes and macrophage colonies were formed by BM and PB cells. Whole agar culture staining revealed that especially macrophage colonies increased in comparison with normal controls. After removal of carbonyl iron-laden cells with a magnet or deprivation of cells adherent to glass from BM cells, the number of macrophage colonies markedly reduced in comparison with the number of colonies formed by untreated BM cells, suggesting that some of the macrophage colony-forming cells (M-CFC) may have phagocytic and/or adherent activity. Radiation sensitivity and thymidine suicide rate of these M-CFC were not different from those of granulocyte colony-forming cells (G-CFC). The predominance of M-CFC in juvenile-type CML may be one of the reflections of fetal-type myelopoiesis since M-CFC are predominant in cord blood and PB in the neonatal period. Moreover, considerable numbers of erythroid-colony-forming units (CFU-E) were present in PB of all patients. It may be concluded that juvenile-type CML is a panmyelopathy with the predominance of M-CFC.
 ...
PMID:Characterization of hemopoietic precursor cells in juvenile-type chronic myelocytic leukemia. 695 Nov 3

In chronic myeloid leukemia (CML) an abnormality at the stem cell level results in unregulated expansion of myeloid progenitors. The mechanism underlying this uncontrolled proliferation remains unclear. An in vitro clonogenic assay which detects the human counterpart of the murine colony forming unit (CFU) CFU-A/CFU-S day 12 was described in a report of our recent findings. CML bone marrow samples were found to proliferate in the CFU-A assay, producing colonies morphologically indistinguishable from normal controls. The bcr/abl transcripts were sought in the RNA from individual colonies using the polymerase chain reaction (PCR). For the five CML samples tested to date, the majority of CFU-A colonies at diagnosis or in early chronic phase were found to be bcr/abl positive. For normal controls both macrophage inflammatory protein-1 alpha (MIP-1 alpha) and transforming growth factor-beta 1 (TGF-beta 1) inhibited the proliferation of CFU-A colonies when directly added to the assay. In contrast, CML progenitors responded normally to TGF-beta 1, but showed no response to MIP-1 alpha. In suicide assays, for five normal bone marrow samples, CFU-A progenitors induced into S-phase returned to a quiescent state after treatment with MIP-1 alpha. CML progenitors demonstrated inherently high cycle status which showed no definite response to MIP-1 alpha. However, TGF-beta 1 resulted in quiescence of CML progenitor cycling. In conclusion, the primitive progenitors from CML samples were inhibited normally by TGF-beta 1 but showed no response to MIP-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Contrasting effects of rh-MIP-1 alpha and TGF-beta 1 on chronic myeloid leukemia progenitors in vitro. 829 72


1 2 Next >>