Philadelphia chromosome‐positive acute lymphoblastic leukemia– current concepts and future perspectives

Faderl, Stefan; Garcia‐Manero, Guillermo; Thomas, Deborah A.; Kantarjian, Hagop M.

doi:10.1046/j.1468-0734.2002.00066.x

Cited by 40 publications

(21 citation statements)

References 89 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The differences between p210-ALL and lymphoblastic CML are historically less clear and have led some to suggest that they represent a single disease entity [23]. However, our data suggest that lymphoblastic CML and p210-ALL are indeed two distinct acute leukemias that can be distinguished largely by patient age at presentation, blast immunophenotype, and cytogenetics.…”

Section: Discussionmentioning

confidence: 73%

The spectrum of adult B‐lymphoid leukemias with BCR‐ABL: Molecular diagnostic, cytogenetic, and clinical laboratory perspectives

et al. 2008

View full text Add to dashboard Cite

The Philadelphia (Ph) chromosome is characteristic of chronic myelogenous leukemia (CML), but it is also the most frequent cytogenetic abnormality in precursor B-lymphoblastic leukemia (ALL) of adults. The vast majority of CML patients have a BCR-ABL translocation that yields a 210 kD (p210) oncoprotein, whereas adult Ph-positive ALL cases can present with either a p190 or a p210 oncoprotein, or both. Considering that 30% of the patients with CML that progress to blast crisis will have a lymphoblastic presentation, adults presenting with a p210 ALL may have either a de novo ALL or CML presenting for the first time in lymphoblastic phase. To identify the distinguishing features, cases of p190-ALL, p210-ALL, and lymphoblastic CML were compared. In spite of significant overlap between the three entities, a number of features were found to aid in their differentiation. p210-ALL patients present at a younger age with blasts that frequently show loss of expression of CD34, whereas p190-ALL patients present with marked increase in peripheral blast percentage. Interestingly, bone marrow findings characteristic of a myeloproliferative disorder are specific, but are not sensitive for lymphoblastic CML. This study suggests that despite the similarities between these leukemias, p190-ALL, p210-ALL, and lymphoblastic phase CML likely represent three distinct diseases. Am. J. Hematol. 83:901-907, 2008. V

show abstract

Section: Discussionmentioning

confidence: 73%

The spectrum of adult B‐lymphoid leukemias with BCR‐ABL: Molecular diagnostic, cytogenetic, and clinical laboratory perspectives

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In this study, we aimed to (i) set up a screening method in order to rapidly identify different Ikaros cDNA transcript variants and (ii) to evaluate their relative expression in samples obtained at diagnosis from 46 adult patients diagnosed with Philadelphia chromosome positive (Ph + ) ALL. Ph + ALL is characterized by clonal proliferation of transformed pre-B cells that express the BCR-ABL oncoprotein; 23 it constitutes 20%-30% of all cases of ALL and has a very poor prognosis. 24,25 Treatment with the tyrosine kinase inhibitor imatinib is currently the standard therapy for CML, which is also caused by BCR-ABL.…”

Section: Introductionmentioning

confidence: 99%

Identification of different Ikaros cDNA transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method

et al. 2008

View full text Add to dashboard Cite

BackgroundIkaros is the prototypic member of a Kruppel-like zinc finger transcription factor subfamily that is required for normal hematopoietic cell differentiation and proliferation, particularly in the lymphoid lineages. Alternative splicing can generate multiple Ikaros isoforms that lack different numbers of exons and have different functions. Shorter isoforms, which lack the amino-terminal domain that mediates sequence-specific DNA binding, exert a dominant negative effect and inhibit the ability of longer heterodimer partners to bind DNA.

show abstract

“…The P210 form of Bcr/Abl is predominantly found in chronic myelogenous leukemia (CML) whereas many Ph-positive acute lymphoblastic leukemia patients have a smaller fusion protein, P190, which shares the same Abl moiety with P210. Phpositive acute lymphoblastic leukemia constitutes f20% of all cases of acute lymphoblastic leukemia and has a very poor prognosis (1,2).…”

Section: Introductionmentioning

confidence: 99%

Resistance to Imatinib of Bcr/Abl P190 Lymphoblastic Leukemia Cells

et al. 2006

View full text Add to dashboard Cite

Around 20% of patients with acute lymphoblastic leukemia are Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia) and express the Bcr/Abl tyrosine kinase. Treatment with the tyrosine kinase inhibitor Imatinib is currently standard for chronic myelogenous leukemia, which is also caused by Bcr/Abl. However, Imatinib has shown limited efficacy for treating Ph-positive acute lymphoblastic leukemia. In our study, we have investigated the effect of Imatinib therapy on murine P190 Bcr/Abl lymphoblastic leukemia cells. Three of four cultures were very sensitive to treatment with 5 Amol/L Imatinib. Significant cell death also initially occurred when the same cultures were treated in the presence of stromal support. However, after 6 days, remaining cells started to proliferate vigorously. The Bcr/Abl tyrosine kinase present in the cells that were now able to multiply in the presence of 5 Amol/L Imatinib was still inhibited by the drug. In concordance with this, the Abl ATP-binding pocket domain of Bcr/Abl in the resistant cells did not contain point mutations which would make the protein Imatinib resistant. The effect of stroma in selecting Imatinibresistant lymphoblasts did not require direct cell-cell contact. SDF-1a could substitute for the presence of stromal cells. Our results show that stroma selects Imatinib-resistant Bcr/Abl P190 lymphoblasts that are less dependent on Bcr/Abl tyrosine kinase activity. Therefore, therapy for Ph-positive acute lymphoblastic leukemia, aimed at interfering with the protective effect of stroma in combination with Imatinib, could be of benefit for the eradication of the leukemic cells. (Cancer Res 2006; 66(10): 5387-93)

show abstract

Philadelphia chromosome‐positive acute lymphoblastic leukemia– current concepts and future perspectives

Cited by 40 publications

References 89 publications

The spectrum of adult B‐lymphoid leukemias with BCR‐ABL: Molecular diagnostic, cytogenetic, and clinical laboratory perspectives

The spectrum of adult B‐lymphoid leukemias with BCR‐ABL: Molecular diagnostic, cytogenetic, and clinical laboratory perspectives

Identification of different Ikaros cDNA transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method

Resistance to Imatinib of Bcr/Abl P190 Lymphoblastic Leukemia Cells

Contact Info

Product

Resources

About