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)

Hematologic changes in panmyelopathia are characterized by a wide-spreading spectrum of symptoms and a rare specifity. Therefore cytological and cytochemical findings do not allow a significant prognosis for the malignant or benign development of panmyelopathia. Cytogenetic experiments showed only the Philadelphia chromosome being of diagnostic value. MEISNER and co-workers, who studied adults with panmyelopathia and proven myelocytic leukemia and 5 children with acute lymphocytic leukemia, found that significant and persistent spontaneous division in unstimulated 24 hr. peripheral blood cultures is an indication of a malignant state. The present work shows that in two of five children with panmyelopathia and with significant spontaneous division chronic myelocytic leukemia developed or was in the very initial state; a third child with spontaneous division is still under control. In contrast to literature only one of 14 children with ALL had significant spontaneous cell division. Therefore the method applied must be checked for its usefulness in ALL and especially for its usefulness in early recognition of a relapse.
 ...
PMID:[Cytogenetic studies as a contribution to the diagnosis of juvenile preleukemia and leukemia recurrence]. 6 24

Myeloblasts from the blood of patients with chronic myeloid leukemia (CML) in a blastoid crisis were shown to have an imbalance in the ribonucleotide pools compared with normal blood neutrophils. This imbalance includes decreased ratios of purine:pyrimidine, adenine:guanine, and uracil:cytosine nucleotides as well as an increased relative concentration and a changed composition of the uridine diphosphate (UDP) sugars, with relatively more UDP-N-acetylhexosamines. Similar, more prominent deviations were found in HL-60 promyelocytic leukemia cell line cells. We have used HL-60 cells to investigate the relationships between these changes in the ribonucleotide pools and myelocyte proliferation, maturation, and/or transformation to the malignant state. When HL-60 cells were separated by elutriation centrifugation into fractions enriched in G1, S phase, or G2 + M, we found only differences in the amount of nucleotides per cell (G2 + M greater than S phase greater than G1) corresponding with the increase in cell volume but not in the qualitative composition of the nucleotides. Therefore, throughout this study, the nucleotide content of all cells was calculated per unit of cell volume. When HL-60 cells were induced to myeloid differentiation with dimethyl sulfoxide, proliferation stopped after 3 days. After 6 days, 70-90% of the cells had matured into cells capable of nitro blue tetrazolium reduction upon stimulation with phorbol myristate acetate. During the maturation process, the mean volume of the HL-60 cells decreased, and the nucleotide content and the purine:pyrimidine and adenine:guanine nucleotide ratios increased. The composition of the UDP sugars changed dramatically, with a decrease of UDP-N-acetylhexosamines and an increase of UDP-hexoses. Similar changes were detected in HL-60 cells that stopped proliferating without dimethyl sulfoxide-induced maturation, except that the UDP sugar composition showed an increase of UDP-N-acetylhexosamines and a decrease of UDP-hexoses. Careful examination of these results indicates that the decreased ratio of purine:pyrimidine nucleotides and the decreased ratio of uracil:cytosine nucleotides observed in CML myeloblasts may be regarded as specific changes caused by transformation of myelocytes to the malignant state. The increased amount of UDP-N-acetylhexosamines and total UDP sugars in the CML cells may also be connected with the transformation process. All other deviations in the nucleotide pattern of transformed myelocytes in comparison to that of mature, normal neutrophils can be explained by the state of proliferation and/or immaturity of CML myeloblasts and HL-60 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Imbalance in the nucleotide pools of myeloid leukemia cells and HL-60 cells: correlation with cell-cycle phase, proliferation, differentiation, and transformation. 346 22

Pulsed nuclear magnetic resonance studies have been carried out on bone marrow of normal human subjects and patients with leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). It was observed that the proton spin-lattice relaxation time (T1) value was discriminatory in the normal and leukemic cases with a statistical significance of (p less than 0.01). Ouabain treatment of cells did not show any perceptible change of T1 value when compared with the nontreated cells, indicating that the concomitant cation effluxes do not affect spin-lattice relaxation time. The water contents of normal, leukemic, and ouabain treated cells were in the range 60%-80%. Higher Fe levels were encountered in the normal than the leukemic samples, while levels of Zn, Cu, Mn, Co, and Ni were elevated in the leukemic samples compared with the normals. Despite the T1 differences observed, the multiparameter studies do not uniquely pinpoint factors responsible for the elevation of T1 in the malignant state.
 ...
PMID:Distinction between normal and leukemic bone marrow by water protons nuclear magnetic resonance relaxation times. 696 35

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.
 ...
PMID:Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias. 1055 51

Dendritic cells (DC) are antigen-presenting cells that can elicit potent antigen-specific responses. Since the development of techniques to cultivate these cells from peripheral blood, there has been a great deal of interest in their use in immunotherapeutic strategies. Here we show that morphologically, phenotypically, and functionally characteristic DC can be generated in vitro from peripheral blood mononuclear cells (PBMC) isolated from frozen apheresis product (AP) of cancer patients. These DC, when pulsed with whole-tumor lysate, protein, or RNA from a chronic myelogenous leukemia (CML) cell line, can induce anti-CML specific cytotoxicity in vitro by autologous cytotoxic T lymphocytes (CTL). RNA and protein-pulsed DC were more effective than lysate-pulsed DC at inducing cytotoxicity at low effector:target (E:T) ratios. These results were comparable to those obtained when fresh healthy peripheral blood was used as the source of PBMC, indicating that neither the malignant state of the patient nor the storage period detrimentally affected the generation or functionality of DC. CML cells were found to increase their level of MHC class I expression after exposure to CTL and pulsed DC thereby becoming better targets. These investigations lend support for the utilization of DC to generate anti-tumor responses in CML.
 ...
PMID:Priming with dendritic cells can generate strong cytotoxic T cell responses to chronic myelogenous leukemia cells in vitro. 1518 38

More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the structural basis of cancer, by identifying the genomic mutations associated with each cancer type. A powerful complementary approach is to systematically characterize the functional basis of cancer, by identifying the genes essential for growth and related phenotypes in different cancer cells. Such information would be particularly valuable for identifying potential drug targets. Here, we report the development of an efficient, robust approach to perform genome-scale pooled shRNA screens for both positive and negative selection and its application to systematically identify cell essential genes in 12 cancer cell lines. By integrating these functional data with comprehensive genetic analyses of primary human tumors, we identified known and putative oncogenes such as EGFR, KRAS, MYC, BCR-ABL, MYB, CRKL, and CDK4 that are essential for cancer cell proliferation and also altered in human cancers. We further used this approach to identify genes involved in the response of cancer cells to tumoricidal agents and found 4 genes required for the response of CML cells to imatinib treatment: PTPN1, NF1, SMARCB1, and SMARCE1, and 5 regulators of the response to FAS activation, FAS, FADD, CASP8, ARID1A and CBX1. Broad application of this highly parallel genetic screening strategy will not only facilitate the rapid identification of genes that drive the malignant state and its response to therapeutics but will also enable the discovery of genes that participate in any biological process.
 ...
PMID:Highly parallel identification of essential genes in cancer cells. 1909 43

Autophagy is an ancient, intracellular degradative system which plays important roles in regulating protein homeostasis and which is essential for survival when cells are faced with metabolic stress. Increasing evidence suggests that autophagy also functions as a tumor suppressor mechanism that harnesses the growth and/or survival of cells as they transition towards a rapidly dividing malignant state. However, the impact of autophagy on cancer progression and on the efficacy of cancer therapeutics is controversial. In particular, although the induction of autophagy has been reported after treatment with a number of therapeutic agents, including imatinib, this response has variously been suggested to either impair or contribute to the effects of anticancer agents. More recent studies support the notion that autophagy compromises the efficacy of anticancer agents, where agents such as chloroquine (CQ) that impair autophagy augment the anticancer activity of histone deacetylase (HDAC) inhibitors and alkylating agents. Inhibition of autophagy is a particularly attractive strategy for the treatment of imatinib-refractory chronic myelogenous leukemia (CML) since a combination of CQ with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) compromises the survival of even BCR-ABL-T315I+ imatinib-resistant CML. Additional studies are clearly needed to establish the clinical utility of autophagy inhibitors and to identify patients most likely to benefit from this novel therapeutic approach.
 ...
PMID:Targeting autophagy: a novel anticancer strategy with therapeutic implications for imatinib resistance. 1970 54