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)

Clonal chromosome disorders occurring or acquired at any postnatal age are often closely related with the origin of tumours. In man the Ph1-chromosome (9; 22) anomaly in CML or the 8; 14 translocation in the African malignant Burkitt Non-Hodgkin lymphoma are, among other cases, prominent examples. On the other hand, constitutive, inherited or novel chromosome anomalies conveyed from the zygote to all tissues of the organism may cause a higher risk for the origin of tumours. Rarely, inheritable minor structural chromosome mutations are known to determine the occurrence of dysontogenetic tumours, as e.g., nephroblastoma, but it is assumed that more such cases will become elucidated in the future. As a special phenomenon, true hydatiform mole is a tumour of the placental tissue due to a disorder of intragenome regulation. Constitutive or numerical structural chromosome anomalies of man are a frequent cause of early or late abortion or of abnormal development and malformation. Despite the predominating principle of selective fetal elimination, a few anomalies such as Down's syndrome, may escape to longer survival due to the relatively mild effects of chromosome 21 triplication. Trisomies which represent in man the most frequent type of chromosome disorders, can be induced, and systematically studied in an experimental model of the mouse. This allows the elaboration of the developmental profiles of all trisomies (and monosomies) of the mouse. Also, the above mentioned principle of selective elimination of abnormal implants can be analysed experimentally. Although the developmental span of a trisomic zygote is limited, there is evidence that cells and tissues isolated from the chromosomally abnormal organism can survive much longer. Thus, haemopoietic stem cells, at least in Ts 12 and 19 of the mouse, can be rescued from trisomic fetuses by transferring them to lethally irradiated adult mice, whose blood forming organs may eventually become permanently repopulated by the trisomic cell lineage. This type of experiments is suited for closer analyses of potential functions vs. defects of chromosomally abnormal cellular systems, e.g., with regard to growth and development.
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PMID:[Chromosome abnormalities, tumours and developmental disorders (author's transl)]. 728 43

In this report an attempt has been made to discuss some of the issues pertinent to myelofibrosis complicating chronic myeloproliferative disorders (CMPDs) that are significantly associated with megakaryocyte function. In this context, biochemical, clinical and particularly morphological features were reviewed. Morphological findings based on elaborate techniques were in keeping with the assumption that in chronic myeloid leukemia (1) the number of CD61-positive megakaryocytes, and in particular their precursors were the parameters most closely associated with myelofibrosis (2) an increased content of reticulin fibers in follow-up biopsies significantly correlated with laboratory data indicative of a high tumor burden (anemia, peripheral blasts, hepatosplenomegaly) and thus a more advanced stage of the disease process (3) even a slight increase in reticulin, i.e. doubling of the normal fiber density was associated with a worse prognosis independent of therapeutic regimens given (4) Dynamics of myelofibrosis was significantly influenced by treatment. In this context, calculation of the myelofibrosis progression index (MPI) revealed a higher score following interferon therapy compared with busulfan. In addition, in idiopathic myelofibrosis (5) the evolution of myelofibrosis was unpredictable and according to the MPI, progression occurred at a relatively low rate (6) proliferation and dilatation of sinusoids accompanying intravascular hematopoiesis and collagen type IV deposits were predominant features in later (fibro-osteosclerotic) stages in the course of disease (7) transmural migration of megakaryocytes demonstrated by three dimensional reconstruction revealed a mole-like tunneling through the thickened sinusoidal wall. A very careful assessment of the numerous correlations between bone marrow features and laboratory data will allow clinicians and pathologists to gain a better insight into the mutual relationships between hematological and morphological findings in CMPDs.
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PMID:Clinicopathological impact of the interaction between megakaryocytes and myeloid stroma in chronic myeloproliferative disorders: a concise update. 908 37

Hereditary cancer syndromes provide excellent models for molecular genetic studies that may aid significantly in case detection, surveillance, and management. Ultimately, molecularly based designer pharmaceuticals may emerge from this research, such as the case of trastuzumab (Herceptin) in HER-2/neu positive breast cancer, and imatinib (Gleevec) in chronic myelocytic leukemia and gastrointestinal stromal tumors. Importantly, these molecular findings may fuel significant clues to cancer control. This background is mentioned since surveillance and management of pancreatic cancer, a major concern of this manuscript, has been uniformly unsuccessful as evidenced by the close correspondence between its incidence and its mortality. Yet knowledge about its genetic and molecular pathology will hopefully ameliorate this vexing problem. One molecular genetic clue is the recently identified palladin mutation in two pancreatic cancer prone families. However, caution must be used toward the palladin mutation, as several recent publications have questioned its significance as a pancreatic cancer causing mutation. We provide a concise description of pancreatic cancer in concert with malignant melanoma in the familial atypical multiple mole melanoma (FAMMM) syndrome as a potential preventive model. This knowledge should help clinicians and basic scientists seize on the opportunity to develop more sensitive and specific screening and management programs in this disease; while a relatively small subset of pancreatic cancer may be readily identifiable through its FAMMM phenotype, coupled with its CDKN2A mutation, this hereditary disorder, given a keen knowledge of its natural history and molecular genetics, may prove to be an effective clinical preventive model.
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PMID:Pancreatic cancer and the FAMMM syndrome. 1799 82