Cytogenetic and Molecular Predictors of Outcome in Acute Lymphocytic Leukemia: Recent Developments

Iacobucci, Ilaria; Papayannidis, Cristina; Lonetti, Annalisa; Ferrari, Anna; Baccarani, Michele; Martinelli, Giovanni

doi:10.1007/s11899-012-0122-5

Cited by 45 publications

(56 citation statements)

References 97 publications

(102 reference statements)

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“…The five major riskstratifying translocations in patients with ALL are BCR-ABL, ETV6-RUNX1, MLL-AF4, SIL-TAL1 and TCF3-PBX1 (Lazic et al, 2010;Iacobucci et al, 2012). The frequency of some of the FO in this study is comparable to the previous studies from Pakistan and other parts of the world (Gaynon et al, 1997;Iacobucci et al, 2012).…”

Section: Discussionsupporting

confidence: 80%

“…This heterogeneity is likely to be due to genetic, racial and geographic variations that exist among different populations (Pui et al, 2003;Treviño et al, 2009;Iacobucci et al, 2012;Schmiegelow et al, 2012;Xu et al, 2012). Therefore, the distribution of genetic and molecular subtypes may not be uniform in different parts of the world (Romana., 1995;Ariffin et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The genetic lesions in ALL play a key role in the abnormal development of lymphoid cells (Kuiper et al, 2007;Treviño et al, 2009;Iacobucci et al, 2012;Xu et al, 2012). The diagnosis of ALL is based on morphology, immunophenotype and cytogenetic analysis of the leukemic blast cells in the peripheral blood and bone marrow (Bhojwani et al, 2012;McGregor et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Chromosomal translocations are powerful prognostic indicators in pediatric ALL (Kuiper et al, 2007;Iacobucci et al, 2012). The presence of recurrent genetic markers represents subtypes of the disease which may have different etiologies (Iqbal et al, 2007;Kuiper et al, 2007;Treviño et al, 2009;Pui et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Awan

Iqbal²,

Aleem³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Awan

Iqbal²,

Aleem³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…In fact, for acute lymphoblastic leukemia, like other malignant conditions, karyotype is one of the prognostic indicators (Borowitz et al, 2008;Iacobucci et al, 2012). Other important prognostic indicators in ALL include age (good prognosis in 1-9 years) (Hilden et al 2006;Tharnprisan et al, 2013), gender (better prognosis in girls) (Pieters and Carroll, 2008), white blood cell count (Landau and Lamanna, 2006) (good prognosis if <50x 10 9 /L at presentation), immunophenotype and minimal residual disease (MRD) detection (Basso et al, 2009) (high relapse risk with MRD of 1% or more at the end of remission induction therapy and those with MRD of 0.1% or more during continuation therapy).…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Abnormalities in Pakistani Children with Acute Lymphoblastic Leukemia

Shaikh¹,

Ali²,

Khurshid³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Cytogenetic abnormalities have important implications in diagnosis and prognosis of acute leukemia and are now considered an important part of the diagnostic workup at presentation. Karyotype, if known at the time of diagnosis, guides physicians to plan appropriate management strategies for their patients. Aim and Objectives: To determine the cytogenetic profile of acute lymphoblastic leukemia (ALL) in Pakistani children in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June 2011 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 153 patients were diagnosed as ALL during the study period, of which 127 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A normal karyotype was present in 51.2% (n=65) of the cases whereas 48.8% (n=62) had an abnormal karyotype. Most of the abnormal cases showed hyperdiploidy(13.4%) followed by t(9;22)(q34;q11.2) (7.08%). Conclusions: This study revealed a relative lack of good prognostic cytogenetic aberrations in Pakistani children with ALL.

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IRS1/β‐Catenin Axis Is Activated and Induces MYC Expression in Acute Lymphoblastic Leukemia Cells

Fernandes

Alves

Machado-Neto

et al. 2017

J of Cellular Biochemistry

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Insulin-like growth factor 1 (IGF1) and its receptor IGF1R regulate normal cell growth and contribute to cell transformation through activation of downstream signaling pathways. In fibroblast cells, insulin receptor substrate 1 (IRS1), through IGF1 signaling, was found to be the key protein for nuclear translocation of β-catenin and MYC transcription activation. We herein investigated the IRS1/β-catenin axis in acute lymphoblastic leukemia (ALL) cells. Samples were obtained from 45 patients with ALL and 13 healthy donors. ALL cell lines were used. Gene expression was measured by quantitative PCR. Protein expression, associations, and cellular localization were evaluated by immunoprecipitation, subcellular fractionation, and confocal microscopy. Cells were submitted to IGF1 stimulation and/or IGF1R pharmacological inhibition (OSI-906). IRS1, β-catenin, and MYC mRNA expression were significantly elevated in ALL patients, compared to normal controls. MYC mRNA expression positively correlated with β-catenin and IRS1. Increased age and MYC expression negatively affected overall survival by univariate analysis. Total and phospho-IGF1R and IRS1, MYC and β-catenin protein expression were higher in ALL cells, compared to normal peripheral blood mononuclear cells (PBMC). IRS1 and β-catenin were found to be colocalized in the nuclei and the cytoplasm of ALL cell lines, whereas both proteins were only slightly detected in the cytoplasm of normal PBMC. In Jurkat cells, a constitutive IRS1 and β-catenin protein interaction were observed; OSI-906 treatment decreased IGF1R tyrosine phosphorylation, IRS1 expression and phosphorylation, nuclear translocation of β-catenin, IRS1 and β-catenin association, and MYC protein expression. In conclusion, the IRS1/β-catenin axis is activated in ALL cells. J. Cell. Biochem. 118: 1774-1781, 2017. © 2016 Wiley Periodicals, Inc.

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Cytogenetic and Molecular Predictors of Outcome in Acute Lymphocytic Leukemia: Recent Developments

Cited by 45 publications

References 97 publications

Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Chromosomal Abnormalities in Pakistani Children with Acute Lymphoblastic Leukemia

IRS1/β‐Catenin Axis Is Activated and Induces MYC Expression in Acute Lymphoblastic Leukemia Cells

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