Modeling the molecular consequences of unbalanced translocations in cancer: Lessons from acute lymphoblastic leukemia.
Authors: Strefford JC, An Q, Harrison CJ
Chromosomal rearrangements are recurrent findings in human cancer and result in aberrant restructuring of the genome. The majority of known fusion genes are the consequence of reciprocal (balanced) translocations. However, most translocations described in human cancer are unbalanced, suggesting that other cancer genes remain to be identified. Historically, it was assumed that these unbalanced rearrangements affected gene function through the loss or gain of chromosomal material. However, emerging data supports direct disruption of genes located at or close to the unbalanced translocation breakpoints. New approaches are required for the identification of those gene loci underlying unbalanced translocations in cancer, as traditional methods have h......
POSTED 06/29/2009 at 02:40 AM --
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Side Effects of Methylphenidate in Childhood Cancer Survivors: A Randomized Placebo-Controlled Trial
CONCLUSIONS: Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials. (Source: PEDIATRICS)...
POSTED 06/28/2009 at 06:00 PM --
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Molecular and chromosomal mutations among children with B-lineage lymphoblastic leukemia in Brazil's Federal District.
Authors: Mesquita DR, Córdoba JC, Magalhães IQ, Córdoba MS, Oliveira JR, Gonçalves A, Ferrari I, Martins-de-Sá C
Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all acute leukemias during childhood. Chromosomal anomalies resulting from gene fusion, which are frequent in leukemias, create hybrid transcripts, the great majority of which encode transcription factors. We analyzed 88 pediatric patients (median age 7.3 years) who had B-lineage acute lymphoblastic leukemia (B-ALL), using reverse transcriptase-polymerase chain reaction, to look for gene fusion transcripts of TEL/AML1, E2A/PBX1, BCR/ABL p190, and MLL/AF4. The frequencies of these transcripts were 21.21, 9.68, 3.03, and 0%, respectively. All positive cases had a common B-ALL immunoph......
POSTED 06/27/2009 at 08:45 PM --
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Prognostic value of miR-16 expression in childhood acute lymphoblastic leukemia relationships to normal and malignant lymphocyte proliferation
Abstract: miR-16, a miRNA involved in cell proliferation and apoptosis regulation, may interfere with either oncogenic or tumor-suppressor pathways and is implicated in leukemogenesis. We then explored its expression in 93 childhood acute lymphoblastic leukemia (ALL) cases. A high miR-16 expression was associated with hyperleukocytosis and poor cytogenetic groups. In the whole group and in B-cell ALLs, disease-free survival (DFS) was significantly shorter for miR-16 above quartile 75. In T-cell ALLs, for both DFS and overall survival, a significant trend was found with a survival shortening from the lowest to the highest miR-16 levels. miR-16 expression neither significantly correlated with normal and malignant lymphocyte proliferation nor varied according to lymphocyte differentiation. Th......
POSTED 06/26/2009 at 09:24 AM --
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Health News of the Day
is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.Study: Overweight People (BMI 25-29.9) Live Longer - Obesity (BMI >30) Linked to Earlier Death. Study: Underweight people (BMI 35) were 36% more likely to die http://bit.ly/GdkdHMayo Clinic Grand Rounds Webcasts http://bit.ly/17R8VJSystemic and intrathecal chemotherapy obviates need for prophylactic CNS irradiation in Acute Lymphoblastic Leukemia http://bit.ly/T0bEeCMS's Landmark Decision on CT Colonography — NEJM Examining the Relevant Data http://bit.ly/95TP250 doctors, health care executives indicted, dozens arrested by FBI in a $50 million Medicare fraud case in Michigan http://bit.ly/......
POSTED 06/26/2009 at 06:59 AM --
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Personalizing chemo for childhood leukemia avoids cranial radiation
Pediatric acute lymphoblastic leukemia is curable without preventive cranial radiation by personalizing chemotherapy, which can improve the cure rate and avoid the use of radiation in acute lymphoblastic leukemia treatment, according to findings in the June 25 issue of the New England Journal of Medicine. (Source: Health Imaging News)...
POSTED 06/25/2009 at 07:07 AM --
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Acute Lymphoblastic Leukemia, The Most Common Childhood Cancer, Is Curable Without Preventive Cranial Radiation
Childhood acute lymphoblastic leukemia (ALL) can be successfully treated using a carefully personalized chemotherapy regimen without cranial radiation, investigators at St. Jude Children's Research Hospital have found. Such radiation of the brain was once a standard ALL treatment to prevent recurrence of the leukemia in the central nervous system (CNS). (Source: Health News from Medical News Today)...
POSTED 06/25/2009 at 04:00 AM --
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Prevalence in Brazil of the (12;21)(p13;q22) translocation in childhood acute lymphoblastic leukemia identified by in situ hybridization with fluorescent DNA probes for the TEL/AML1 rearrangement
We report a case of PV with evolution to AML in which it was possible to demonstrate the two-hit model of leukemogenesis: one mutation confers proliferative advantage and another interferes with differentiation. Case: A 55-year-old female patient was diagnosed with PV in 2002 and treated with phlebotomies and hydroxyurea. In 2006, there was progression topost-polycythemic fibrosis with AML one year later. She presented the JAK2V617F mutation. The result of karyotyping performed at diagnosis was normal and at transformation, 46,XX,del(20)(q13.1) was detected in 4/20 metaphases. FISH analysis of a stored sample for 20q13 showed the deletion in 20% of interphases confirming the earlier presence of a clonal abnormality that was not detected by karyotyping. The JAK2V617F mutation is sufficient ......
POSTED 06/25/2009 at 02:43 AM --
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Impact of allogeneic haematopoietic stem cell transplantation in the outcome of Ph+ acute lymphoblastic leukaemia treated with an imatinib-containing regimen
(Source: British Journal of Haematology)...
POSTED 06/24/2009 at 06:00 PM --
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Discordance of MLL-rearranged (MLL-R) infant acute lymphoblastic leukemia in monozygotic twins with spontaneous clearance of preleukemic clone in unaffected twin
We report the first case of discordance in an infant monozygotic twin pair. Twin A presented at age 9 months with MLL-ENL+ acute lymphoblastic leukemia and twin B remains healthy 3 years later. The presence and eventual clearance of a clonal population of MLL-ENL+ cells was shown in the bone marrow and peripheral blood of twin B. Clearance of this clone was temporally associated with viral-induced cytopenias, suggesting an immune-mediated clearance of the clone before the development of leukemia. Thus, concordance of MLL-rearranged acute leukemia in infant monozygotic twins is not universal. The implications of this case for MLL-rearranged leukemogenesis are discussed. (Source: Blood)...
POSTED 06/24/2009 at 06:00 PM --
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TGF-{beta} induces degradation of TAL1/SCL by the ubiquitin-proteasome pathway through AKT-mediated phosphorylation
In this report we show that the intracellular concentration of TAL1 is regulated by transforming growth factor β (TGF-β), which triggers its polyubiquitylation and degradation by the proteasome. This effect is mediated by AKT1, which phosphorylates TAL1 at threonine 90. Immunoprecipitation experiments showed that this event increases association of TAL1 with the E3 ubiquitin ligase CHIP. The E47 heterodimerization partner of TAL1 hinders this association. Our observations indicate that activation of the TGF-β and phosphatidylinositol 3-kinase/AKT pathways might reverse overexpression of TAL1 in leukemic cells by inducing proteolysis of this important oncogene. (Source: Blood)...
POSTED 06/24/2009 at 06:00 PM --
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Childhood leukemia curable without cranial radiation
Children with acute lymphoblastic leukemia can be successfully treated without exposure to cranial radiation, investigators at St. Jude Children's Research Hospital report in the June 25 issue of the New England Journal of Medicine. (Source: AuntMinnie.com Headlines)...
POSTED 06/24/2009 at 05:01 PM --
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Optimized Chemo Can Eliminate Cranial Irradiation in Childhood ALL (CME/CE, with audio)
SAN FRANCISCO (MedPage Today) -- Even high-risk childhood acute lymphoblastic leukemia (ALL) can be safely treated without prophylactic cranial irradiation when using personalized chemotherapy, researchers found. (Source: MedPage Today Hematology/Oncology)...
POSTED 06/24/2009 at 04:15 PM --
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Cranial Radiation Can Be Omitted in Childhood Acute Lymphoblastic Leukemia
Childhood acute lymphoblastic leukemia can be successfully treated using personalized chemotherapy without cranial radiation. Medscape Medical News (Source: Medscape Hematology-Oncology Headlines)...
POSTED 06/24/2009 at 09:08 AM --
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Pediatric acute lymphoblastic leukemia is curable without preventive cranial radiation
(St. Jude Children's Research Hospital) Childhood acute lymphoblastic leukemia can be successfully treated using a carefully personalized chemotherapy regimen without cranial radiation, investigators at St. Jude Children's Research Hospital have found. (Source: EurekAlert! - Cancer)...
POSTED 06/23/2009 at 11:00 PM --
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Cranial Irradiation in Pediatric Leukemia Unnecessary
In children newly diagnosed with acute lymphoblastic leukemia, effective risk-adjusted chemotherapy
may eliminate the need for prophylactic cranial irradiation, according to a study published in the June 25 issue of
the New England Journal of Medicine. (Source: Modern Medicine)...
POSTED 06/23/2009 at 06:00 PM --
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ORIGINAL ARTICLE: Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation
This large trial of acute lymphoblastic leukemia in children aimed to determine whether intensive systemic and intrathecal chemotherapy could obviate the need for prophylactic central nervous system irradiation, which is associated with distressing late complications. The results show that, with meticulous monitoring of responses and toxic effects, it is possible not only to avoid cranial irradiation but also to improve the overall outcome. (Source: New England Journal of Medicine)...
POSTED 06/23/2009 at 06:00 PM --
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Acute lymphoblastic leukemia, the most common childhood cancer, is curable without preventive cranial radiation
Childhood acute lymphoblastic leukemia (ALL) can be successfully treated using a carefully personalized chemotherapy regimen without cranial radiation, investigators at St. Jude Children's Research Hospital have found. Such radiation of the brain was once a standard ALL treatment to prevent recurrence of the leukemia in the central nervous system (CNS). (Source: St. Jude Children's Research Hospital)...
POSTED 06/23/2009 at 06:00 PM --
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The impact of risk stratification by early bone-marrow response in childhood lymphoblastic leukaemia: results from the United Kingdom Medical Research Council trial ALL97 and ALL97/99
The 1997 acute lymphoblastic leukaemia (ALL) trial (ALL97) was a randomised comparison of prednisolone versus dexamethasone and of 6-mercaptopurine versus 6-thioguanine. During the first 2 years of the trial, review of survival data showed the preceding trial, UKALL XI, was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups. The therapy template was therefore altered to an American Children's Cancer Group (CCG) style regimen, including stratification by age, white cell count and early response to therapy by assessment of the bone marrow. This phase of the trial was designated ALL97/99. Comparison of the two phases showed that the event-free survival (EFS) for both ALL97 and ALL97/99 wa......
POSTED 06/21/2009 at 06:00 PM --
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Adult B lymphoblastic leukaemia / lymphoma with hypodiploidy (-9) and a novel chromosomal translocation t(7;12)(q22;p13) presenting with severe eosinophilia - case report and review of literature
We describe a rare presentation of acute lymphoblastic leukemia in a young adult male who had vague and minimal symptoms with mild splenomegaly. There was severe eosinophilia along with absence of blasts in the peripheral blood, and 40% blasts with increase in eosinophils in the bone marrow. The blasts were positive for common precursor B cell markers on flow cytometry. The patient had a unique cytogenetic abnormality t(7;12)(q22;p13),-9, not previously described in acute lymphoblastic leukemia. He was categorized as poor risk due to failure to achieve complete remission after induction with UK ALL XII chemotherapy. (Source: Journal of Hematology and Oncology)...
POSTED 06/20/2009 at 06:00 PM --
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