Posted by rob on June 30, 2009 under Uncategorized | 
Authors: Kibel AS
Recurrent gene fusions, typically associated with hematological malignancies and rare bone and soft-tissue tumors, have recently been described in common solid tumors. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to “re-discover” the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukemia cell line and the TMPRSS2-ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeras transcripts in cancer cell lines and tumors. Taken together, this study establishes a robust pipeline for th…
Posted by rob on under Uncategorized |
Recurrent gene fusions, typically associated with hematological malignancies and rare bone and soft-tissue tumors, have recently been described in common solid tumors. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to “re-discover” the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukemia cell line and the TMPRSS2-ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeras transcripts in cancer cell lines and tumors. Taken together, this study establishes a robust pipeline for the discovery of nov…
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Posted by rob on June 27, 2009 under Uncategorized |
This study investigates the mechanisms responsible for increased Rac2 gene expression during myeloid cell differentiation. Treatment of K562 chronic myelogenous leukemia cells with phorbol-12-myristate-13-acetate (PMA) induces megakaryocytic differentiation and Rac2 gene transcription following a lag of 6-12 h. Promoter/luciferase reporter gene assays reveal that a 135 bp cis-element located between -4223 and -4008 bp upstream of the Rac2 transcription start site is necessary and sufficient for PMA-induced gene expression. The AP1 transcription factor binds to three cis-elements within the 135 bp Rac2 gene regulatory region both in vitro and in vivo following PMA treatment, and mutagenesis of the AP1 binding sites ablates the PMA responsiveness of the 135 bp Rac2 gene regulatory region. Ov…
Posted by rob on June 26, 2009 under Uncategorized |
Chronic myelogenous leukemia (CML) is caused by rearrangement of the BCR-ABL oncogene. Imatinib inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. However, 10–15% of patients with chronic-phase CML fail imatinib therapy because of primary or secondary resistance . The selective BCR-ABL inhibitor, nilotinib, was designed to fit into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib . In addition to being more potent than imatinib against wild-type BCR-ABL, nilotinib is significantly more active against most imatinib-resistant BCR-ABL mutants . The most common non-hematologic toxicities of nilotinib have been rash, pruritus, headache, nausea, and fatigue, with hyperbilirubinemia being a fre…
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Posted by rob on under Uncategorized |
We report here a case of refractory cytopenia with mutilineage dysplasia (RAEB-1) with monosomy 7 which rapidly transformed into AML in a patient with GIST during imatinib treatment. (Source: Leukemia Research)
Posted by rob on under Uncategorized |
Abstract: Allogeneic stem cell transplantation is considered to be a curative treatment modality in patients with chronic myelogenous leukemia. However patients are at risk for relapse years after transplantation. Currently we present two patients who relapsed 16 and 24 years after allogeneic bone marrow transplantation, respectively. These patients emphasize the need for long term follow-up of such patients. (Source: Leukemia Research)
Posted by rob on June 25, 2009 under Uncategorized |
We present mature results in 335 patients with CML who underwent allogeneic bone marrow transplantation (BMT) from HLA-identical siblings following busulfan and cyclophosphamide (BU/Cy2). Two hundred twenty-nine were in chronic phase (CP) and 106 in accelerated or blastic phase at transplantation. Median follow-up exceeded 14 years. The estimated probability of 18-year leukemia-free survival (LFS) for CP patients was 55.6% and for those beyond CP, 10.5%. Of 182 patients who survived leukemia-free at 3 years, the estimated probability of LFS at 18 years was 61.9%. Late relapse (P = .039) and late NRM (P = .008) occurred at higher rates in patients beyond CP at transplantation. There was no plateau in LFS. (Source: Biology of Blood and Marrow Transplantation)
Posted by rob on June 22, 2009 under Uncategorized |
The objective of this study was to evaluate and compare neurocognitive changes in patients with chronic myelogenous leukemia (CML) or primary myelodysplastic syndrome (MDS) after allogeneic HSCT or other therapies.In this prospective cohort study, serial evaluations of attention, concentration, memory, mood, and quality of life were used in a consecutive sample of 106 eligible patients who had CML (n = 91) or MDS (n = 15) at enrollment and then 12 months and 18 months after HSCT or other therapy.The 3 evaluations at enrollment, 12 months, and 18 months were completed by 98%, 95%, and 89% of surviving participants, respectively. Among all patients, there was significant improvement in memory over 18 months. For example, the 45 patients who underwent HSCT (42 patients with CML and 3 patients…
Posted by rob on June 21, 2009 under Uncategorized |
Authors: Wei YL, Liang Y, Xu L, Zhao XY
Imatinib mesylate is effective against Ph chromosome-positive leukemia; however, resistance has been reported. High expression of bcr-abl in mRNA and protein levels, and other alterations were found in patients who experienced imatinib treatment failures and thus it is important to design alternative treatment strategies. The aim of this study was to evaluate the in vitro effect of berbamine, on imatinib-resistant chronic myelogenous leukemia (CML) K562 (K562-r) cells, and explore the mechanisms. The growth of K562-r cells was examined using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Morphological analysis and DNA agarose electrophoresis were used to detect apoptosis in K562-r cells, and the extent of the cells …
Posted by rob on June 16, 2009 under Uncategorized |
Imatinib is the current standard frontline therapy for chronic myelogenous leukemia (CML). In the majority of patients, imatinib induces a complete cytogenetic response (CCyR); however, complete molecular responses are infrequent. The Bcr-Abl fusion creates a unique sequence of amino acids that could constitute a target for immunomodulation.A mixture of heteroclitic and native peptides derived from both b3a2 and b2a2 sequences was used to vaccinate patients with CML in CCyR who were receiving imatinib therapy and who had stable Bcr-Abl transcript levels.Ten patients were enrolled, all with b2a2 transcripts (including 2 patients who had coexpression of b2a2 and b3a2). Patients had received imatinib for a median of 62 months. Three of 10 patients achieved 1-log reduction in Bcr-Abl transcrip…
Posted by rob on June 14, 2009 under Uncategorized |
Schwannomas, although benign, can be fatal or give rise to significant morbidity due to an unpredictable growth rate. They can reoccur after surgery or radiation, current treatments each with significant inherent risks. These risks are further amplified in neurofibromatosis type 2 (NF2), a germ line predisposition syndrome characterized by multiple schwannomas, underlying the need for biological targeted therapies. Gleevec (STI571, imatinib mesylate), in addition to the bcr-abl oncogene in chronic myelogenous leukemia, inhibits c-kit and platelet-derived growth factor receptor (PDGFR) signaling, thereby expanding its use to several malignant and benign human diseases. In the present study, we show that human sporadic and NF2-associated schwannomas have increased expression along with activ…
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Posted by rob on June 9, 2009 under Uncategorized |
I wanted to let all of you in the CML group know that my father Robert Wood Neill has passed away. Many of you who are long term members know that the CML group was started many years in the days long before Gleevec when my mother Laquita was diagnosed with CML.
During the past 2 years my mother Laquita and I along with a team of caregivers have spent 24 hours a day taking care of my father as his health declined. We started out 2 years ago with a diagnosis of lung cancer which my father overcame but his health declined due to dementia, TIA’s, pneumonia and various other complications.
When he first became ill 2 years ago his physician offered nothing more than saying he should be admitted to a nursing home. My mother Laquita did an extraordinary job the past 2 years in taking care of my father despite having CML herself. We had a wonderful team of home health aides, nurses, therapists, and others who provided 24 hour home care he was able to enjoy a good quality of life up until the last few days and he never had to sign up for hospice.
If any of you would like to read the obituary and sign the guestbook it is online at the link below.
http://ofhwinona.com/LeeObit5.html
Rob
Posted by rob on June 1, 2009 under Uncategorized |
A 15-year-old male with congenital HIV infection was diagnosed with chronic myelogenous leukemia (CML) at age 4 years 9 months. HIV was initially treated with zidovudine. For the last >10 years he has received didanosine, lamivudine, and nelfinavir. CML was treated with Interferon alfa (INF-[alpha]) for >10 years and a brief course of hydroxyurea (HU). He remained in chronic phase CML since diagnosis however recent molecular monitoring revealed increased BCR/ABL transcripts necessitating a change in therapy to imatinib. The very prolonged chronic phase of CML in this patient has been unexpected especially in light of the underlying congenital HIV infection. Pediatr Blood Cancer. © 2009 Wiley-Liss, Inc. (Source: Pediatric Blood and Cancer)
