Ponatinib in the leukemia world: why a reevaluation is necessary for Philadelphia chromosome-positive patients with T315I mutation.

Posted by rob on May 20, 2015 under Uncategorized | Comments are off for this article

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Ponatinib in the leukemia world: why a reevaluation is necessary for Philadelphia chromosome-positive patients with T315I mutation.

Expert Rev Hematol. 2014 Oct;7(5):513-5

Authors: Goodrich AD

Abstract

Strategic drug design is used to meet the needs of numerous diseases for which there is no other recourse. Take the T315I mutation, for example, which occurs in Philadelphia chromosome-positive leukemias and renders all currently available tissue kinase inhibitors useless. The US FDA therefore saw it fit to avail ponatinib, the therapeutic result of careful drug design, to patients based on early data. However, its sales and marketing were later suspended due to emerging safety concerns. This drug has now returned to market albeit with tighter labeling. While the lesson for early approvals may be to restrict the drug to as narrow a patient population as possible, the potential benefits of this drug for the target population must not be lost amidst the controversy.

PMID: 25199408 [PubMed - indexed for MEDLINE]

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Toxic Erythema of Chemotherapy Following Leukemia Cutis.

Posted by rob on May 16, 2015 under Uncategorized | Comments are off for this article

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Toxic Erythema of Chemotherapy Following Leukemia Cutis.

J La State Med Soc. 2014 Nov-Dec;166(6):236-238

Authors: Kaskas N, DiGiorgio C, Vincent B, Walia S, Mermilliod J

Abstract

A 56-year-old Caucasian male newly diagnosed with acute myelogenous leukemia (AML) M3 presented with a six-week history of multiple painful erythematous nodules scattered on his trunk and extremities, previously treated as abscesses with incision and drainage plus oral trimethoprim-sulfamethoxazole without improvement. A punch biopsy was performed, and the histopathology and immunostaining profile were compatible with leukemia cutis secondary to AML. Induction chemotherapy for AML with cytarabine, etoposide, and mitoxantrone was initiated. Dermatology was reconsulted two weeks later for evaluation and treatment of a new eruption on both dorsal hands and wrists that began three days after starting induction chemotherapy. On physical exam, there were well-demarcated erythematous patches and plaques with mild induration on the hands, extending onto the distal forearms and sparing the dorsal metacarpalphalangeal joints and ventral wrists. Biopsy findings were consistent with toxic erythema of chemotherapy, likely secondary to cytarabine.

PMID: 25978658 [PubMed - as supplied by publisher]

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Molecular genetic evaluation of myeloproliferative neoplasms.

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Molecular genetic evaluation of myeloproliferative neoplasms.

Int J Lab Hematol. 2015 May;37 Suppl 1:61-71

Authors: Azzato EM, Bagg A

Abstract

The classical myeloproliferative neoplasms (MPNs) consist of chronic myelogenous leukemia (CML) and the non-CML MPNs, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Molecular testing plays a crucial role in each of these disease entities. In this review, we discuss the role and caveats of BCR-ABL1 fusion transcript evaluation in CML diagnosis and monitoring, as well as ABL1 kinase mutation testing in the setting of tyrosine kinase inhibitor resistance. We also focus on JAK2, MPL, and CALR mutations in PV, ET, and PMF.

PMID: 25976962 [PubMed - in process]

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Distinguishing clonal evolution from so-called secondary acute myelogenous leukemia: Adhering to unifying concepts of the genetic basis of leukemogenesis.

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Distinguishing clonal evolution from so-called secondary acute myelogenous leukemia: Adhering to unifying concepts of the genetic basis of leukemogenesis.

Blood Cells Mol Dis. 2015 Jun;55(1):1-2

Authors: Lichtman MA

PMID: 25976458 [PubMed - in process]

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Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report.

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Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report.

J Med Case Rep. 2014;8:295

Authors: Caocci G, Greco M, La Nasa G

Abstract

INTRODUCTION: Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up.

CASE PRESENTATION: We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug.

CONCLUSION: Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therapy.

PMID: 25194418 [PubMed - indexed for MEDLINE]

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A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.

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A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.

Sci Transl Med. 2014 Sep 3;6(252):252ra121

Authors: Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, Zhu LJ, Hutchinson L, Cerny J, Khoury HJ, Sheng Z, Druker BJ, Li S, Green MR

Abstract

Resistance to the BCR-ABL inhibitor imatinib mesylate (IM) poses a major problem for the treatment of chronic myeloid leukemia (CML). IM resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, in many instances, there is no mutation in BCR-ABL, and the basis of such BCR-ABL-independent IM resistance remains to be elucidated. To gain insight into BCR-ABL-independent IM resistance mechanisms, we performed a large-scale RNA interference screen and identified IM-sensitizing genes (IMSGs) whose knockdown renders BCR-ABL(+) cells IM-resistant. In these IMSG knockdown cells, RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling is sustained after IM treatment because of up-regulation of PRKCH, which encodes the protein kinase C (PKC) family member PKC?, an activator of CRAF. PRKCH is also up-regulated in samples from CML patients with BCR-ABL-independent IM resistance. Combined treatment with IM and trametinib, a U.S. Food and Drug Administration-approved MEK inhibitor, synergistically kills BCR-ABL(+) IMSG knockdown cells and prolongs survival in mouse models of BCR-ABL-independent IM-resistant CML. Finally, we showed that CML stem cells contain high levels of PRKCH, and this contributes to their intrinsic IM resistance. Combined treatment with IM and trametinib synergistically kills CML stem cells with negligible effect on normal hematopoietic stem cells. Collectively, our results identify a therapeutically targetable mechanism of BCR-ABL-independent IM resistance in CML and CML stem cells.

PMID: 25186176 [PubMed - indexed for MEDLINE]

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Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.

Posted by rob on May 15, 2015 under Uncategorized | Comments are off for this article

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Misfolding, Aggregation, and Disordered Segments in c-Abl and p53 in Human Cancer.

Front Oncol. 2015;5:97

Authors: de Oliveira GA, Rangel LP, Costa DC, Silva JL

Abstract

The current understanding of the molecular mechanisms that lead to cancer is not sufficient to explain the loss or gain of function in proteins related to tumorigenic processes. Among them, more than 100 oncogenes, 20-30 tumor-suppressor genes, and hundreds of genes participating in DNA repair and replication have been found to play a role in the origins of cancer over the last 25?years. The phosphorylation of serine, threonine, or tyrosine residues is a critical step in cellular growth and development and is achieved through the tight regulation of protein kinases. Phosphorylation plays a major role in eukaryotic signaling as kinase domains are found in 2% of our genes. The deregulation of kinase control mechanisms has disastrous consequences, often leading to gains of function, cell transformation, and cancer. The c-Abl kinase protein is one of the most studied targets in the fight against cancer and is a hotspot for drug development because it participates in several solid tumors and is the hallmark of chronic myelogenous leukemia. Tumor suppressors have the opposite effects. Their fundamental role in the maintenance of genomic integrity has awarded them a role as the guardians of DNA. Among the tumor suppressors, p53 is the most studied. The p53 protein has been shown to be a transcription factor that recognizes and binds to specific DNA response elements and activates gene transcription. Stress triggered by ionizing radiation or other mutagenic events leads to p53 phosphorylation and cell-cycle arrest, senescence, or programed cell death. The p53 gene is the most frequently mutated gene in cancer. Mutations in the DNA-binding domain are classified as class I or class II depending on whether substitutions occur in the DNA contact sites or in the protein core, respectively. Tumor-associated p53 mutations often lead to the loss of protein function, but recent investigations have also indicated gain-of-function mutations. The prion-like aggregation of mutant p53 is associated with loss-of-function, dominant-negative, and gain-of-function effects. In the current review, we focused on the most recent insights into the protein structure and function of the c-Abl and p53 proteins that will provide us guidance to understand the loss and gain of function of these misfolded tumor-associated proteins.

PMID: 25973395 [PubMed]

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CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus.

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CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus.

Med Oncol. 2014 Aug;31(8):112

Authors: Wang J, Huang T, Sun J, Yu Y, Liu Z, Li W, Jia J, Chen C

Abstract

To detect the expression of cancerous inhibitor of phosphatase 2A (CIP2A) in chronic myelocytic leukemia (CML) and investigate the mechanism underlying CIP2A knockdown-mediated cell proliferation and apoptosis as well as the interaction of CIP2A with breakpoint cluster region-Abelson leukemia virus (BCR-ABL). CIP2A mRNA and protein expression in chronic myelocytic leukemia-chronic (CML-CP) patients and healthy controls were determined by RT-PCR and Western blot. In vivo, c-Myc expression, PP2A activity, cell proliferation, and apoptosis of CML cells were detected with CIP2A depletion. In addition, the relationship among CIP2A, BCR-ABL, and tyrosine phosphatase SHP-1 was explored by depleting/overexpressing CIP2A or inhibiting BCR-ABL. The level of CIP2A mRNA was higher in CML-CP patients than healthy controls (56/74, 75.7 % vs. 1/35, 2.9 %, P < 0.001), and CIP2A protein was overexpressed in corresponding specimens. CIP2A knockdown by siRNA reduced the level of c-Myc protein and clonogenic formation, inhibited the activity of PP2A, K562 cell proliferation, and promoted cell apoptosis. Suppressing BCR-ABL by imatinib mesylate (IM) significantly decreased CIP2A expression. CIP2A knockdown decreased BCR-ABL but increased SHP-1 expression, and CIP2A overexpression had the reverse effect. CIP2A is overexpressed in CML-CP patients, and its expression may promote CML pathogenesis. CIP2A and BCR-ABL can regulate each other in a positive feedback loop. CIP2A may be a useful therapeutic target in CML-CP, particularly in patients with IM resistance. However, further studies are needed to validate the interaction between CIP2A and BCR-ABL using other tyrosine kinase inhibitors than IM.

PMID: 25023053 [PubMed - indexed for MEDLINE]

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Rhodococcus equi pneumonia and sepsis in an allogeneic haematopoietic stem cell transplant recipient.

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Rhodococcus equi pneumonia and sepsis in an allogeneic haematopoietic stem cell transplant recipient.

BMJ Case Rep. 2014;2014

Authors: Shahani L

Abstract

Rhodococcus equi is an aerobic facultative intracellular organism that is known to infect cells of the macrophage-monocyte lineage. It is a common veterinary pathogen; however, the incidence of this infection in humans has risen and it has been recognised as an emerging opportunistic pathogen among the immunocompromised patients. We present the case of a patient with chronic myeloid leukaemia who had received allogenic stem cell transplant and presented to the hospital with clinical picture of pneumonia. Her condition worsened on initial broad spectrum antimicrobials and 3?weeks into her hospitalisation, R. equi was isolated from her broncheoalveolar lavage and blood cultures. Based on the susceptibility, therapy was changed to four active antimicrobials; however, the patient failed to improve and eventually died. This case highlights the importance of considering the diagnosis of R. equi among immunosuppressed patients early in the right clinical setting due to the high virulence associated with this organism.

PMID: 24943142 [PubMed - indexed for MEDLINE]

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Imatinib mesylate-induced pseudoporphyria in two children.

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Imatinib mesylate-induced pseudoporphyria in two children.

Pediatr Dermatol. 2014 Sep-Oct;31(5):603-7

Authors: Mahon C, Purvis D, Laughton S, Bradbeer P, Teague L

Abstract

Imatinib mesylate was the first of several tyrosine kinase inhibitors approved for use in the treatment of a number of human cancers. Adverse cutaneous reactions to imatinib are common. Pseudoporphyria has been infrequently reported in adults undergoing imatinib therapy for chronic myeloid leukemia. We present two children with pseudoporphyria induced by imatinib therapy for hematologic malignancies. In view of the burgeoning use of imatinib in children, physicians should be aware that pseudoporphyria may develop as a consequence of imatinib therapy.

PMID: 24920470 [PubMed - indexed for MEDLINE]

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Treatment of Chronic Myelogenous Leukemia by Blocking Cytokine Alterations Found in Normal Stem and Progenitor Cells.

Posted by rob on May 13, 2015 under Uncategorized | Comments are off for this article

Treatment of Chronic Myelogenous Leukemia by Blocking Cytokine Alterations Found in Normal Stem and Progenitor Cells.

Cancer Cell. 2015 May 11;27(5):671-681

Authors: Welner RS, Amabile G, Bararia D, Czibere A, Yang H, Zhang H, Pontes LL, Ye M, Levantini E, Di Ruscio A, Martinelli G, Tenen DG

Abstract

Leukemic cells disrupt normal patterns of blood cell formation, but little is understood about the mechanism. We investigated whether leukemic cells alter functions of normal hematopoietic stem and progenitor cells. Exposure to chronic myelogenous leukemia (CML) caused normal mouse hematopoietic progenitor cells to divide more readily, altered their differentiation, and reduced their reconstitution and self-renewal potential. Interestingly, the normal bystander cells acquired gene expression patterns resembling their malignant counterparts. Therefore, much of the leukemia signature is mediated by extrinsic factors. Indeed, IL-6 was responsible for most of these changes. Compatible results were obtained when human CML were cultured with normal human hematopoietic progenitor cells. Furthermore, neutralization of IL-6 prevented these changes and treated the disease.

PMID: 25965572 [PubMed - as supplied by publisher]

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Convert and Conquer: The Strategy of Chronic Myelogenous Leukemic Cells.

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Convert and Conquer: The Strategy of Chronic Myelogenous Leukemic Cells.

Cancer Cell. 2015 May 11;27(5):611-613

Authors: Méndez-Ferrer S, García-Fernández M, de Castillejo CL

Abstract

Emerging evidence is contributing to explain how leukemias disrupt normal blood cell production. In this issue of Cancer Cell, Welner and colleagues show that, during the development of chronic myeloid leukemia, mutated cells transform normal hematopoietic progenitors into “leukemic like” cells through IL-6 secretion, proposing a new cellular target.

PMID: 25965567 [PubMed - as supplied by publisher]

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Calibration of BCR-ABL1 mRNA quantification methods using genetic reference materials is a valid strategy to report results on the international scale.

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Calibration of BCR-ABL1 mRNA quantification methods using genetic reference materials is a valid strategy to report results on the international scale.

Clin Biochem. 2014 Sep;47(13-14):1333-6

Authors: Mauté C, Nibourel O, Réa D, Coiteux V, Grardel N, Preudhomme C, Cayuela JM, GBMHM

Abstract

OBJECTIVES: Until recently, diagnostic laboratories that wanted to report on the international scale had limited options: they had to align their BCR-ABL1 quantification methods through a sample exchange with a reference laboratory to derive a conversion factor. However, commercial methods calibrated on the World Health Organization genetic reference panel are now available. We report results from a study designed to assess the comparability of the two alignment strategies.

DESIGN AND METHODS: Sixty follow-up samples from chronic myeloid leukemia patients were included. Two commercial methods calibrated on the genetic reference panel were compared to two conversion factor methods routinely used at Saint-Louis Hospital, Paris, and at Lille University Hospital. Results were matched against concordance criteria (i.e., obtaining at least two of the three following landmarks: 50, 75 and 90% of the patient samples within a 2-fold, 3-fold and 5-fold range, respectively).

RESULTS: Out of the 60 samples, more than 32 were available for comparison. Compared to the conversion factor method, the two commercial methods were within a 2-fold, 3-fold and 5-fold range for 53 and 59%, 89 and 88%, 100 and 97%, respectively of the samples analyzed at Saint-Louis. At Lille, results were 45 and 85%, 76 and 97%, 100 and 100%, respectively. Agreements between methods were observed in the four comparisons performed.

CONCLUSION: Our data show that the two commercial methods selected are concordant with the conversion factor methods. This study brings the proof of principle that alignment on the international scale using the genetic reference panel is compatible with the patient sample exchange procedure. We believe that these results are particularly important for diagnostic laboratories wishing to adopt commercial methods.

PMID: 24915631 [PubMed - indexed for MEDLINE]

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Prognostic value of regulatory T cells in newly diagnosed chronic myeloid leukemia patients.

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Prognostic value of regulatory T cells in newly diagnosed chronic myeloid leukemia patients.

Int J Clin Oncol. 2014 Aug;19(4):753-60

Authors: Zahran AM, Badrawy H, Ibrahim A

Abstract

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal disease, characterized by a reciprocal t(9, 22) that results in a chimeric BCR/ABL fusion gene. Regulatory T cells (Tregs) constitute the main cell population that enables cancer cells to evade immune surveillance.

OBJECTIVE: The purpose of our study was to investigate the level of Tregs in newly diagnosed CML patients and to correlate it with the patients’ clinical, laboratory and molecular data. We also aimed to assess the effect of treatment using tyrosine kinase inhibitor (TKI) on Treg levels.

METHODS: Tregs were characterized and quantified by flow cytometry in 63 newly diagnosed CML patients and 40 healthy controls. TKI was used in 45 patients with chronic phase CML, and the response to therapy was correlated with baseline Treg levels.

RESULTS: The percentages of Tregs were significantly increased in CML patients compared to the controls. Treg numbers were significantly lower in patients with chronic phase CML versus the accelerated and blast phases, and were significantly lower in patients with complete molecular remission (CMR) compared to those patients without CMR.

CONCLUSION: Tregs may play a role in the maintenance of CML. Moreover, the decrease of their levels in patients with CMR suggests that Tregs might have a clinical value in evaluating the effects of therapy.

PMID: 24068564 [PubMed - indexed for MEDLINE]

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Chronic Myelogenous Leukemia in Eastern Pennsylvania: An Assessment of Registry Reporting.

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Chronic Myelogenous Leukemia in Eastern Pennsylvania: An Assessment of Registry Reporting.

J Registry Manag. 2015;42(1):9-11

Authors: Mertz KJ, Buchanich JM, Washington TL, Irvin-Barnwell EA, Woytowitz DV, Smith RE

Abstract

BACKGROUND: Chronic myelogenous leukemia (CML) has been reportable to the Pennsylvania Cancer Registry (PCR) since the 1980s, but the completeness of reporting is unknown. This study assessed CML reporting in eastern Pennsylvania where a cluster of another myeloproliferative neoplasm was previously identified.

METHODS: Cases were identified from 2 sources: 1) PCR case reports for residents of Carbon, Luzerne, or Schuylkill County with International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes 9875 (CML, BCR-ABL+), 9863 (CML, NOS), and 9860 (myeloid leukemia) and date of diagnosis 2001-2009, and 2) review of billing records at hematology practices. Participants were interviewed and their medical records were reviewed by board-certified hematologists.

RESULTS: PCR reports included 99 cases coded 9875 or 9863 and 9 cases coded 9860; 2 additional cases were identified by review of billing records. Of the 110 identified cases, 93 were mailed consent forms, 23 consented, and 12 medical records were reviewed. Hematologists confirmed 11 of 12 reviewed cases as CML cases; all 11 confirmed cases were BCR/ABL positive, but only 1 was coded as positive (code 9875).

CONCLUSIONS: Very few unreported CML cases were identified, suggesting relatively complete reporting to the PCR. Cases reviewed were accurately diagnosed, but ICD-0-3 coding often did not reflect BCR-ABL-positive tests. Cancer registry abstracters should look for these test results and code accordingly.

PMID: 25961786 [PubMed - as supplied by publisher]

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Coexpression Pattern Analysis of NPM1-Associated Genes in Chronic Myelogenous Leukemia.

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Coexpression Pattern Analysis of NPM1-Associated Genes in Chronic Myelogenous Leukemia.

Biomed Res Int. 2015;2015:610595

Authors: Wang F, Chan LW, Tsui NB, Wong SC, Siu PM, Yip SP, Yung BY

Abstract

Background. Nucleophosmin 1 (NPM1) plays an important role in ribosomal synthesis and malignancies, but NPM1 mutations occur rarely in the blast-crisis and chronic-phase chronic myelogenous leukemia (CML) patients. The NPM1-associated gene set (GCM_NPM1), in total 116 genes including NPM1, was chosen as the candidate gene set for the coexpression analysis. We wonder if NPM1-associated genes can affect the ribosomal synthesis and translation process in CML. Results. We presented a distribution-based approach for gene pair classification by identifying a disease-specific cutoff point that classified the coexpressed gene pairs into strong and weak coexpression structures. The differences in the coexpression patterns between the normal and the CML groups were reflected from the overall structure by performing two-sample Kolmogorov-Smirnov test. Our developed method effectively identified the coexpression pattern differences from the overall structure: P??value = 1.71 × 10(-22) < 0.05 for the maximum deviation D = 0.109. Moreover, we found that genes involved in the ribosomal synthesis and translation process tended to be coexpressed in the CML group. Conclusion. Our developed method can identify the coexpression difference between two different groups. Dysregulation of ribosomal synthesis and translation process may be related to the CML disease. Our significant findings may provide useful information for the novel CML mechanism exploration and cancer treatment.

PMID: 25961029 [PubMed - in process]

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Nutritionally variant streptococci bacteremia in cancer patients: a retrospective study, 1999-2014.

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Nutritionally variant streptococci bacteremia in cancer patients: a retrospective study, 1999-2014.

Mediterr J Hematol Infect Dis. 2015;7(1):e2015030

Authors: Yacoub AT, Krishnan J, Acevedo IM, Halliday J, Greene JN

Abstract

BACKGROUND: Nutritionally variant Streptococci (NVS), Abiotrophia and Granulicatella are implicated in causing endocarditis and blood stream infections more frequently than other sites of infection. Neutropenia and mucositis are the most common predisposing factors for infection with other pathogens in cancer patients. In this study, we investigated the clinical characteristics of NVS bacteremia in cancer patients and identified risk factors and outcomes associated with these infections.

MATERIALS AND METHODS: We retrospectively reviewed all cases of NVS bacteremia occurring from June 1999 to April 2014 at H. Lee Moffitt Cancer Center and Research Institute. The computerized epidemiology report provided by the microbiology laboratory identified thirteen cancer patients with NVS bacteremia. We collected data regarding baseline demographics and clinical characteristics such as age, sex, underlying malignancy, neutropenic status, duration of neutropenia, treatment, and outcome.

RESULTS: Thirteen patients were identified with positive NVS blood stream infection. Ten patients (77%) had hematologic malignancies, including chronic lymphocytic leukemia (CLL)(1), multiple myeloma (MM)(1), acute myelogenous leukemia (AML)(4), and non-Hodgkin’s lymphoma (NHL)(4). The non-hematologic malignancies included esophageal cancer(2) and bladder cancer (1).

CONCLUSION: NVS should be considered as a possible agent of bacteremia in cancer patients with neutropenia and a breach in oral, gastrointestinal and genitourinary mucosa (gingivitis/mucositis).

PMID: 25960858 [PubMed]

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Appearance of Acute Myelogenous Leukemia (AML) in a Patient with Breast Cancer after Adjuvant Chemotherapy: Case Report and Review of the Literature.

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Appearance of Acute Myelogenous Leukemia (AML) in a Patient with Breast Cancer after Adjuvant Chemotherapy: Case Report and Review of the Literature.

Iran J Cancer Prev. 2015 Mar-Apr;8(2):125-8

Authors: Payandeh M, Khodarahmi R, Sadeghi M, Sadeghi E

Abstract

Acute Myelogenous Leukemia (AML) is an aggressive hematologic malignancy that cause by abnormal proliferation and accumulation of hematopoietic progenitor cells. A 37-year-old woman referred to oncologic clinic with a self-detected mass and pain in her left breast. The stage of tumor was ???A. She was treated with the combination of anthracycline and cyclophosphamide for four courses, followed by four courses of paclitaxel with trastuzumab for one year. After 18 months of the first treatment for breast cancer, her bone marrow biopsy was compatible with AML-M2. Here, we are reporting a young woman case with breast cancer that developed AML malignancy during short interval of therapy.

PMID: 25960852 [PubMed]

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IDH1, Lipid Metabolism and Cancer: Shedding New Light on Old Ideas.

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IDH1, Lipid Metabolism and Cancer: Shedding New Light on Old Ideas.

Biochim Biophys Acta. 2015 May 7;

Authors: Bogdanovic E

Abstract

BACKGROUND: Since the initial discovery of mutations in the isocitrate dehydrogenase 1 (IDH1) gene in a large subset of human low-grade gliomas and acute myelogenous leukemia (AML), much interest focused on the function of IDH1 and on the relationship between mutations in IDH1 and tumour progression. To date, mutations in the IDH1 gene have been found in numerous cancers with the highest frequencies occurring in gliomas, chondrosarcomas/enchondromas and cholangiocarcinomas.

SCOPE OF REVIEW: IDH1 was first described in the scientific literature as early as 1950. Early researchers proposed that the enzyme likely functions in cellular lipid metabolism based on the observation that the enzymatic reaction produces NADPH and partially localizes to peroxisomes. This article highlights the studies implicating IDH1 in cytoplasmic and peroxisomal lipid metabolism from the early researchers to the recent studies examining mutant IDH1(R132), the most common IDH1 mutation found in cancer.

MAJOR CONCLUSIONS: While a role for IDH1 in lipid biosynthesis in the liver and adipose tissue is now established, a role in lipid metabolism in the brain and tumours is beginning to be examined. The recent discoveries that IDH1(R132H) interferes with the metabolism of phospholipids in gliomas and that IDH1 activity could participate in the synthesis of acetyl-CoA from glutamine in hypoxic tumours highlights roles for IDH1 in lipid metabolism in a broad spectrum of tissues.

GENERAL SIGNIFICANCE: Interferences in cytoplasmic and peroxisomal lipid metabolism by IDH1(R132) may contribute to the more favourable clinical outcome in patients whose tumours express mutations in the IDH1 gene.

PMID: 25960387 [PubMed - as supplied by publisher]

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Myeloid sarcoma as the initial presentation of chronic myelogenous leukemia, medullary chronic phase in era of tyrosine kinase inhibitors: A report of 11 cases.

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Myeloid sarcoma as the initial presentation of chronic myelogenous leukemia, medullary chronic phase in era of tyrosine kinase inhibitors: A report of 11 cases.

Am J Hematol. 2015 May 11;

Authors: Chen Z, Wang W, Rich A, Tang G, Hu S

PMID: 25960187 [PubMed - as supplied by publisher]

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