BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features.
BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.
Dept. of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. nina-rosa.neuendorff@charite.de.
Nina Rosa
NR
Neuendorff
Dept. of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Labor Berlin Charité-Vivantes GmbH, Sylter Str. 2, 13353, Berlin, Germany.
Thomas
T
Burmeister
Dept. of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Labor Berlin Charité-Vivantes GmbH, Sylter Str. 2, 13353, Berlin, Germany.
Bernd
B
Dörken
Dept. of Hematology, Oncology and Tumor Immunology, Charité - University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Labor Berlin Charité-Vivantes GmbH, Sylter Str. 2, 13353, Berlin, Germany.
Jörg
J
Westermann
D000208:Acute Disease; D000465:Algorithms; D003937:Diagnosis, Differential; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014944:World Health Organization; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D016044:Fusion Proteins, bcr-abl
Acute myeloid leukemia; BCR-ABL; Chronic myeloid leukemia; Tyrosine kinase inhibitor