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

An unusual case of chronic myeloid leukemia presenting to the gynecological unit as a case of septic abortion is presented. Though history and clinical examination suggested the possibility of double pathology of septic abortion and chronic myeloid leukemia, histology of the products removed from the uterus showed it to be leukemic deposits. The diagnosis of leukemia was confirmed by marrow aspiration (trephine biopsy). Careful clinical examination and systematic investigation helped in diagnosing the pathology and to treat her appropriately.
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PMID:Chronic myeloid leukemia presenting as a gynecological emergency. 347 17

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

Chronic granulocytic leukemia (CGL) was diagnosed in the second trimester of pregnancy in a mother of four, who decided to terminate the pregnancy immediately. According to the literature this unusual combination is not a definite indication for abortion since CGL does not adversely affect the course of the pregnancy nor the pregnancy alter the course of the disease. Prudent treatment with busulfan or splenic irradiation, when indicated, apparently does not endanger the development of the fetus.
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PMID:Chronic granulocytic leukemia in pregnancy. A case report and review of the literature. 745 5

Hematologic neoplasms diagnosed during pregnancy, present significant difficulties in patient management. Besides the strictly medical facts, moral, ethical and religious issues should be strongly considered. For the optimal management of individual situations an integrated multidisciplinary approach is mandatory. Hodgkin's disease, acute leukemias, non Hodgkin's lymphoma and less frequently chronic myelogenous leukemia have been reported in pregnant women. Curative treatment for most of these diseases include intensive chemotherapy regimens. Potential damage to the fetus is a major concern, due to the teratogenic effects of antimetabolites, alkylating agents and radiation therapy. Effect of pregnancy in each of these neoplasms is discussed. Although some rules of management exist, dangerous generalizations should be avoided. Particular obstetric considerations such as timing of delivery, and therapeutic abortion should be carried out on an individual basis. The emotional impact of the situation must not be underestimated.
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PMID:[Hematologic neoplasms and pregnancy]. 756 54

Hydroxyurea is classified as an S-phase antineoplastic agent (pregnancy category D). Two women became pregnant while taking hydroxyurea for sickle cell anemia and delivered live infants with no congenital anomalies. Although teratogenic effects of hydroxyurea were reported in animal studies, several case reports suggest the agent may have minimal teratogenic effects on the developing fetus. Fourteen cases of hydroxyurea therapy in pregnant patients with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease are reported in the literature. Three pregnancies were terminated by elective abortion; one woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. Further studies with larger numbers of patients receiving hydroxyurea during pregnancy, with longer follow-up of exposed children and more careful assessment of fetotoxic effects, are required before the agent can be promoted as safe in pregnancy.
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PMID:Hydroxyurea in two pregnant women with sickle cell anemia. 1060 98

The management of pregnant patients with chronic myeloproliferative disorders (MPD) is a difficult problem. Patients with essential thrombocythaemia (ET), and, less frequently, those with chronic myeloid leukaemia (CML) or polycythaemia vera (PV), present at a childbearing age. Pregnancy itself does not appear to affect adversely the natural course and prognosis of the MPD. However, fertility might be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. It ET, first-trimester abortion is the most frequent complication but increased perinatal mortality and premature delivery are also observed. Placental infarction due to thrombosis seems to be the most consistent event. Maternal thrombotic or haemorrhagic complications are rare but are more common than seen in normal pregnancy. The outcome of pregnancy seems to be positively influenced by aspirin, at least in some cases. The value of cytoreduction and/or heparin prophylaxis has not been established but may have a role in selected cases. In CML, the potential adverse effects of hyperleukocytosis, and sometimes thrombocytosis, generally make myelosuppressive treatment essential. In PV, the number of reported pregnancies is low. Maintaining the PCV below 0.45 is of the utmost importance relating to the outcome of pregnancy. Although cytoreductive drugs should generally be avoided, if possible, until at least after the first trimester of pregnancy, interferon-alpha seems to be the drug of choice when myelosuppression is indicated. In summary, the available information about pregnancy occurring during the course of an MPD indicates that successful management of pregnancy is possible. However, optimal management of these patients is poorly defined and agreed protocols are not available. In view of these problems, it is timely to consider the establishment of a national or European registry to monitor prospectively the management offered to pregnant women found to have an MPD.
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PMID:Fertility, pregnancy and the management of myeloproliferative disorders. 1064 Feb 21

Essential thrombocythemia (ET) and chronic myelogenous leukemia (CML) usually present with distinctive features. Citing experience with cases that overlap, the Polycythemia Vera Study Group recommends that negative tests for the Philadelphia chromosome be obtained before diagnosing ET. We describe two young women presenting with features absolutely typical for ET, including extreme thrombocytosis, no leukocytosis, no basophilia, no peripheral immature cells, and no splenomegaly. Severe thrombotic complications ensued: multiple cerebrovascular thromboemboli, pulmonary emboli, and miscarriage in one and myocardial infarction in the other. By 4 years, both developed leukocytosis, extreme basophilia, and circulating blasts, typical of accelerated CML. Cytogenetic studies were then performed, revealing the Philadelphia chromosome. Imatinib produced rapid clearing of blasts and basophils, but one woman later succumbed after allogeneic bone marrow transplant and the other has not achieved a major cytogenetic response. We conclude that CML can present in identical fashion as ET. The mandate for routine Philadelphia chromosome testing is magnified by the availability of targeted therapy and its greater efficacy in early stage disease.
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PMID:Every case of essential thrombocythemia should be tested for the Philadelphia chromosome. 1560 81

Centrosomes play fundamental roles in mitotic spindle organization, chromosome segregation and maintenance of genetic stability. Recently, we have shown that centrosome aberrations occur early in chronic myeloid leukemia (CML) and are induced by imatinib in normal fibroblasts in vitro. To investigate the influence of BCR-ABL on centrosomes, we performed long-term in vitro experiments employing the conditionally p210BCR-ABL-expressing (tetracycline-inducible promoter) human monocytic cell line U937p210BCR-ABL/c6 as a model of CML chronic phase. Centrosome hypertrophy was detectable after 4 weeks of transgene expression onset, increasing up to a rate of 25.7% aberrant cells within 13 weeks of propagation. This concurred with clonal expansion of aneuploid cells displaying a hyperdiploid phenotype with 57 chromosomes. Partial reversibility of centrosome aberrations (26-8%) was achieved under prolonged propagation (14 weeks) after abortion of induction and bcr-abl silencing using small interfering RNA. Therapeutic doses of imatinib did not revert the aberrant phenotype, but counteracted the observed reverting effect of bcr-abl gene expression switch off. Suggesting a mechanistic model that features distinct abl-related tyrosine kinase activity levels as essential determinants of centrosomal integrity, this is the first report mechanistically linking p210BCR-ABL oncoprotein activity to centrosomal hypertrophy.
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PMID:Expression of the p210BCR-ABL oncoprotein drives centrosomal hypertrophy and clonal evolution in human U937 cells. 1759 4

Women are advised not to attempt pregnancy while on hydroxyurea (HU) due to the teratogenic effects of this agent, based on results obtained from animal studies. Several case reports suggest that HU may have minimal or no teratogenic effects on the developing human fetus. Fourteen cases of HU therapy in pregnant patients diagnosed with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease (SCD) have been reported. Three pregnancies were terminated by elective abortion; 1 woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. We contend that case studies such as these have too few patients and cannot effectively address the adverse effect of HU on preimplantation embryo or fetuses. The objective of this study was to assess the risks associated with a clinically relevant dose of HU used for the treatment of SCD, on ovulation rate and embryo development, using adult C57BL/6J female mice as a model. In Experiment 1, adult female mice were randomly assigned to a treatment or a control group (N = 20/group). Treatment consisted of oral HU (30 mg/kg) for 28 days; while control mice received saline (HU vehicle). Five days to the cessation of HU dosing, all mice were subjected to folliculogenesis induction with pregnant mare serum gonadotropin (PMSG). Five mice/group were anesthetized at 48 hours post PMSG to facilitate blood collection via cardiac puncture for estradiol-17beta (E(2)) measurement by RIA. Ovulation was induced in the remaining mice at 48 hours post PMSG with human chorionic gonadotropin (hCG) and immediately caged with adult males for mating. Five plugged female mice/group were sacrificed for the determination of ovulation rate. The remaining mated mice were sacrificed about 26 hours post hCG, ovaries excised and weighed and embryos harvested and cultured in Whitten's medium (WM) supplemented with CZBt. In Experiments 2 and 3, (N = 10/Experiment) folliculogenesis and ovulation were induced in untreated mice followed by mating. Recovered embryos were either exposed continuously (Experiment 2) or intermittently (Experiment 3) to bioavailable HU (18 microg HU/mL of WM + CZBt) or WM + CZBt only (control). Treated mice sustained decreased ovarian wt, ovulation rate and circulating E(2) compared with controls (P < 0.05). Fewer embryos retrieved from HU-treated mice developed to blastocyst stage (32%) compared with those from controls (60%; P < 0.05). Furthermore, continuous or intermittent in vitro exposures of embryos to HU also resulted in reduced development to blastocyst stage (continuous HU, 9 vs. control, 63%; P < 0.05; intermittent HU, 20 vs. control, 62%; P < 0.05) with embryos exposed continuously to HU in vitro fairing worse. Even though HU is well tolerated, our data suggest that it compromises folliculogenesis and the ability of generated embryos to develop. Therefore, designed studies with larger numbers of patients receiving HU during pregnancy, with longer follow-up of exposed children and more careful assessment of embryo/fetotoxic effects, are required before this agent can be promoted as safe in pregnancy.
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PMID:Perturbation of the developmental potential of preimplantation mouse embryos by hydroxyurea. 2062 9

We presented our experience in chronic myeloid leukemia (CML) patients who conceived children and/or became pregnant while receiving tyrosine kinase inhibitor (TKI). Among 7 male patients, 7 pregnancies resulted in the birth of 7 healthy babies. Among 18 female patients, 8 ended in elective abortion; 3 had spontaneous abortion, and 7 carried to term, resulting in the birth of 8 healthy babies. All children have normal growth and development. All patients remain in TKI therapy and in good response. It is suggested that female patients are advised to practice adequate contraception. No special precautions apply for male patients receiving TKI.
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PMID:Pregnancies in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitor. 2393 84


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