scholarly journals Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 136-141
Author(s):  
J van Denderen ◽  
D van der Plas ◽  
T Meeuwsen ◽  
N Zegers ◽  
W Boersma ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Leukemia Cell ◽  
Polyclonal Antiserum ◽  
Leukemic Cells ◽  
Specific Marker ◽  
Leukemia Cell Lines

Philadelphia (Ph′)-positive acute lymphoblastic leukemia (ALL) is highly associated with two forms of chimeric bcr-abl proteins: P190bcr- abl and P210bcr-abl. Whereas P210bcr-abl also occurs in chronic myeloid leukemia, P190bcr-abl is uniquely expressed in Ph′-positive ALL. As a consequence, P190bcr-abl is preeminently a tumor-specific marker in leukemic cells of ALL patients. Because P190bcr-abl is composed of the normal bcr and abl proteins, the major part of the P190bcr-abl molecule comprises nontumor-specific determinants. The joining region between bcr and abl, newly generated during the Ph′ translocation, is exclusively a tumor-specific epitope on the P190bcr-abl molecule. Therefore, only antibodies against the bcr-abl joining region will detect the tumor-specificity of P190bcr-abl. In this study a polyclonal antiserum, termed BP-ALL, was raised against a synthetic peptide corresponding to the bcr-abl junction in P190bcr-abl. The reactivity of BP-ALL with native P190bcr-abl derived from a Ph′-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis. BP-ALL reacted highly specifically with P190bcr-abl but not with P210bcr-abl isolated from chronic myeloid leukemia cell lines. Peptide inhibition studies further confirmed the fine specificity of BP-ALL. Our data indicate that the tumor-specific bcr-abl junction domain is exposed in an antigenic fashion on the P190bcr-abl molecule.

scholarly journals Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 136-141 ◽  
Author(s):  
J van Denderen ◽  
D van der Plas ◽  
T Meeuwsen ◽  
N Zegers ◽  
W Boersma ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Leukemia Cell ◽  
Polyclonal Antiserum ◽  
Leukemic Cells ◽  
Specific Marker ◽  
Leukemia Cell Lines

Abstract Philadelphia (Ph′)-positive acute lymphoblastic leukemia (ALL) is highly associated with two forms of chimeric bcr-abl proteins: P190bcr- abl and P210bcr-abl. Whereas P210bcr-abl also occurs in chronic myeloid leukemia, P190bcr-abl is uniquely expressed in Ph′-positive ALL. As a consequence, P190bcr-abl is preeminently a tumor-specific marker in leukemic cells of ALL patients. Because P190bcr-abl is composed of the normal bcr and abl proteins, the major part of the P190bcr-abl molecule comprises nontumor-specific determinants. The joining region between bcr and abl, newly generated during the Ph′ translocation, is exclusively a tumor-specific epitope on the P190bcr-abl molecule. Therefore, only antibodies against the bcr-abl joining region will detect the tumor-specificity of P190bcr-abl. In this study a polyclonal antiserum, termed BP-ALL, was raised against a synthetic peptide corresponding to the bcr-abl junction in P190bcr-abl. The reactivity of BP-ALL with native P190bcr-abl derived from a Ph′-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis. BP-ALL reacted highly specifically with P190bcr-abl but not with P210bcr-abl isolated from chronic myeloid leukemia cell lines. Peptide inhibition studies further confirmed the fine specificity of BP-ALL. Our data indicate that the tumor-specific bcr-abl junction domain is exposed in an antigenic fashion on the P190bcr-abl molecule.

scholarly journals Epidemiologic study on survival of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5271-5278 ◽  
Author(s):  
Franck E. Nicolini ◽  
Michael J. Mauro ◽  
Giovanni Martinelli ◽  
Dong-Wook Kim ◽  
Simona Soverini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutation Detection ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Epidemiologic Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
T315i Mutation

Abstract The BCR–ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome—positive (Ph)+ acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph+ ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection.

Different Kinetic Pattern of Chronic Myeloid Leukemia: Lymphoblastic and Myeloblastic Blastic Crisis

1980 ◽  
Vol 66 (3) ◽  
pp. 295-303
Author(s):  
Wanda Piacibello ◽  
Massimo Aglietta ◽  
Felice Gavosto
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Kinetic Studies ◽  
Leukemic Cells ◽  
Cell Kinetic ◽  
Blastic Crisis ◽  
Kinetic Pattern

Cell kinetic studies were performed in 8 ease of lymphoid blastic crisis (BC) of chronic myeloid leukemia at the onset of BC and during subsequent relapses. The results were compared with those found in 7 myeloblastic BC. While in the myeloblastic transformation the labeling index (LI) was always higher in bone marrow than in peripheral blood blasts, suggesting a predominant bone marrow proliferation of the leukemic cells, in the lymphoid transformation a higher LI was often found in peripheral blasts. Moreover, the lymphoblastic transformations were frequently characterized by lymphadenopathy. These findings point to the similarities between lymphoid BC and acute lymphoblastic leukemia, suggesting the possibility that a blastic event may originate in an extramedullary site and that an extramedullary BC is more likely to be lymphoid in nature.

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