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)

Candida arthritis is quite rare and might be caused either by direct intra-articular inoculation of Candida or secondary to hematogeneous seeding of Candida in immunocompromised hosts. Until now less than 50 cases of Candida arthritis have been reported in the literature. We report a case of Candida arthritis, which occurred in a patient with chronic myelogenous leukemia (CML) in blastic transformation. Aggressive chemotherapy and broad-spectrum antibiotics for a prolonged period for febrile neutropenia had been given to the patient. Arthritis of the left knee appeared during the recovery phase of leukopenia. Despite treatment with fluconazole, no clinical or microbiological improvement was obtained. Thus, administration of liposomal amphotericin B was started and after 3 days there was improvement. We can conclude that fluconazole might not be sufficient in some Candida arthritis cases and liposomal amphotericin B might be a good alternative in these resistant cases.
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PMID:Candida arthritis in a patient with chronic myelogenous leukemia (CML) in blastic transformation, unresponsive to fluconazole, but treated effectively with liposomal amphotericin B. 1237 55

Chronic myeloid leukemia (CML) is caused by the constitutively active Bcr-Abl tyrosine kinase. This fusion protein is generated by the Philadelphia translocation t(9;22). CML is a progressive condition that invariably advances from a drug-sensitive to a drug-resistant, aggressive, acute leukemia. The mechanisms responsible for this progression are largely unknown; however, in many cases, progression is accompanied by an increase in Bcr-Abl expression. Osteopontin (OPN) expression has been shown to be involved in the progression and increased aggression and invasiveness of many solid tumors. Here, we demonstrate that OPN expression is induced in a model of leukemia, and we describe the identification of specific signaling pathways required for the induction of OPN expression by p210 Bcr-Abl. We have determined that high levels of Bcr-Abl activate a signaling cascade involving the sequential activation of Ras, phosphatidylinositol-3 kinase, atypical protein kinase C, Raf-1, and mitogen-activated protein kinase kinase, leading to the ultimate expression of OPN. Our results suggest that these molecules represent a single pathway and also that there is no redundancy in this pathway, as inhibition of any individual component results in a block in the induction of OPN. The data presented here define for the first time the ability of Bcr-Abl to stimulate the expression of OPN and also identify the signaling pathway involved. This may not only prove important in understanding the mechanisms of progression of CML but also highlights a pathway that may prove significant in many other cases of oncogenesis, where OPN expression is implicated.
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PMID:Bcr-Abl regulates osteopontin transcription via Ras, PI-3K, aPKC, Raf-1, and MEK. 1585 38

Therapeutic agents for chronic myeloid leukaemia (CML) in the chronic phase include hydroxyurea, interferon alpha, allogeneic stem cell transplantation and the tyrosine kinase inhibitor imatinib (STI 571, Gleevec). For elderly patients, oral hydroxyurea is suitable for the relief of symptoms caused by hyperleukocytosis, and splenic irradiation would be considered if abdominal discomfort or fullness induced by splenomegaly were present. Tumour lysis syndrome (TLS) is seldom seen in the treatment for CML, and TLS caused by hydroxyurea or splenic irradiation is rarely observed. Herein, we report an elderly CML patient who received treatment with hydroxyurea, allopurinol, hydration and splenic irradiation. After 3 days, acute TLS developed. Aggressive supportive treatment, including haemodialysis, stabilized the condition.
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PMID:Hydroxyurea and splenic irradiation-induced tumour lysis syndrome: a case report and review of the literature. 1633 96

Despite recent success in the treatment of early-stage disease, blastic phase (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge. The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression. To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays. Supervised microarray data analysis revealed 114 differentially expressed genes (P<10(-4)), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were downregulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-time-polymerase chain reaction and flow cytometry. Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy.
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PMID:Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. 1661 18

The development of a de novo lymphoma in patients affected by chronic myelogenous leukemia (CML) is a rare event. The introduction of new molecular cytogenetic techniques, such as fluorescence in situ hybridization (FISH), allows a correct differential diagnosis between lymphoid blastic crisis and a blastoid variant of mantle cell lymphoma (MCL), which shows an aggressive behavior and some molecular characteristics detectable by cytogenetics and immunohistochemistry. We report a case of a blastoid variant of MCL that developed in a patient with CML who achieved complete cytogenetic and molecular response to imatinib mesylate treatment.
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PMID:Blastoid mantle cell lymphoma occurring in a patient in complete remission of chronic myelogenous leukemia. 1735 81

Condyloma acuminata or genital warts are caused by human papilloma virus (HPV). Ongoing proliferation of HPV in patients with congenital or acquired immunodeficiency states leads to the development of rapidly progressive and sometimes locally invasive tumor with or without dysplasia. Aggressive treatment, diagnostic immuno-typing, and follow-up are necessary in patients with ongoing immunosuppression. We report a case of giant ano-genital condylomatosis due to HPV types 6 and 11 in a patient with chronic myeloid leukemia after allogeneic bone marrow transplantation. The tumor was successfully treated with surgical excision and local application of 5% imiquimod cream.
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PMID:Giant anal condylomatosis after allogeneic bone marrow transplantation: a rare complication of human papilloma virus infection. 1751 21

The treatment of chronic myelogenous leukemia (CML) has been revolutionized by the development of the small-molecule tyrosine kinase inhibitor imatinib. The primary target for this drug is the oncogenic BCR-ABL kinase. Five-year survival rates for patients in chronic phase CML is now greater than 80%. Patients who have advanced beyond the chronic phase to the accelerated phase or blast crisis, however, have not faired as well. Progression occurs for a variety of reasons, including late diagnosis, slow response to imatinib, and the development of imatinib-resistant clones. Imatinib resistance has, in part, been addressed with the introduction of the new BCR-ABL inhibitors, namely dasatinib and nilotinib. These drugs have shown efficacy in CML patients with wild-type BCR-ABL and some BCR-ABL mutants that are imatinib-resistant. Unfortunately, some BCR-ABL mutations remain resistant to these therapies and will require the development of alternative treatments, and other mechanisms of imatinib resistance besides BCR-ABL mutation exist. In the future, genetic and pharmacologic tests may allow the clinician to predict response to imatinib. More aggressive therapies are being considered for high-risk patients, including increased dosage of the current tyrosine kinase inhibitors, along with combination therapies. Aggressive therapy holds promise, as the data suggest that responses are improved. Unfortunately, toxicities are also increased, and thus a balance must be found to ensure safety and compliance. This is especially important for young CML patients, who hopefully will remain in remission for decades. Polymerase chain reaction analysis has become of primary importance as a means of assessing disease burden, and given the idiosyncrasies of this technique, standards must be established to allow results to be compared across different institutions. Additionally, the nature of advanced disease is being explored. Intriguingly, genetic analysis of transformed blasts from patients in blast crisis has identified numerous members of the Wnt/B-catenin pathway and JunB as being activated. Increased activity of these pathways correlates with poor response and eventual disease progression. In addition to these data, evidence is emerging associating survival of the quiescent blast cell with Wnt activity, leading to the hope that Wnt inhibitors will increase the likelihood of eradicating these cells. Other areas such as microRNA profiling and DNA methylation patterns are likely to provide important information.
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PMID:Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia. 1834 28

Mechanical properties play an important role in regulating cellular activities and are critical for unlocking the mysteries of life. Atomic force microscopy (AFM) enables researchers to measure mechanical properties of single living cells under physiological conditions. Here, AFM was used to investigate the topography and mechanical properties of red blood cells (RBCs) and three types of aggressive cancer cells (Burkitt's lymphoma Raji, cutaneous lymphoma Hut, and chronic myeloid leukemia K562). The surface topography of the RBCs and the three cancer cells was mapped with a conventional AFM probe, while mechanical properties were investigated with a micro-sphere glued onto a tip-less cantilever. The diameters of RBCs are significantly smaller than those of the cancer cells, and mechanical measurements indicated that Young's modulus of RBCs is smaller than those of the cancer cells. Aggressive cancer cells have a lower Young's modulus than that of indolent cancer cells, which may improve our understanding of metastasis.
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PMID:Atomic force microscopy imaging and mechanical properties measurement of red blood cells and aggressive cancer cells. 2316 Aug 28

Many effective therapeutic options are available for patients with chronic myelogenous leukemia (CML). Imatinib, a first-generation tyrosine kinase inhibitor (TKI), is one of several options for patients who present with CML, whether in chronic phase, accelerated phase, or blast crisis. Although CML is very responsive to the selective TKIs, with response rates in chronic phase of greater than 90%, unusual presentations have been documented. Response rates for patients with CML in accelerated phase and blast crisis are notably lower to both first- and second-generation TKIs. This report presents a recent case of a young woman with newly diagnosed CML who presented with an accelerated phase isolated central nervous system (CNS) relapse after standard imatinib therapy, who initially experienced a complete hematologic response. Further treatment options, and monitoring of disease response, are discussed. Aggressive strategies, such as intrathecal chemotherapy, change in tyrosine kinase inhibitor to one with increased CNS penetration, and consideration of allogenic stem cell transplantation, are potential therapeutic modalities. Prophylaxis of the CNS in patients deemed at risk is an area requiring further study.
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PMID:An unusual presentation of chronic myelogenous leukemia: a review of isolated central nervous system relapse. 2384 13

Chronic myelogenous leukemia (CML) in children is relatively rare. Because of a lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate that some genetic differences exist in pediatric and adult CML. Because children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid lifelong exposure to TKIs and their associated adverse effects. Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.
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PMID:Pediatric chronic myeloid leukemia is a unique disease that requires a different approach. 2651 Nov 35


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