Contributions
Abstract: PB1614
Type: Publication Only
Background
The cryptic translocation t(12;21)(p13;q22) and the respective ETV6-RUNX1 fusion gene, is the most common genetic abnormality in childhood acute lymphoblastic leukemia (ALL), accounting for 20%>25% of the cases, while it is a very rare finding in adolescents and adults with ALL, with an incidence of ≤1%. Additional chromosome abnormalities are detected in more than two thirds of cases, however the t(4;9)(q21;p24) has not been reported so far. This abnormality that results in the formation of SEC31A-JAK2 fusion gene has been previously reported as the first recurrent JAK2-associated translocation in classical Hodgkin lymphoma. To the best of our knowledge only two other cases of t(4;9)(q21;p24) have been reported so far – in a patient with ALL, with unknown ETV6-RUNX1 status and in a patient with undifferentiated lung carcinoma.
Aims
To present for the first time a rare case of t(4;9)(q21;p24) in an adolescent with a molecularly defined ETV6-RUNX1-positive B-ALL.
Methods
A 19-old male was admitted to the hospital because of pancytopenia and elevated serum lactate dehydrogenase levels, tested in relation to complaints of acute thoracic back pain.
Results
On admission, the physical exam was unremarkable. The initial laboratory tests revealed white blood cell counts of 1.6x109/l with no blasts; a hemoglobin level of 90 g/l and platelet counts of 10x109/l. On aspirate smear, the bone marrow was markedly hypercellular with a subtotal infiltration with lymphoblasts. Flow cytometry of bone marrow detected a blast cells population accounting for 48.3% of all cells with the following phenotype: Syto41+/CD45dim+/CD19+/CD10+/ CD20-/CD34+/CD38+/ CD58+. Conventional cytogenetic analysis demonstrated an abnormal karyotype: 45,XY,-4, der(9)t(4;9)(q21;p24),14ps+[5]/46,XY,14ps+[15], while molecular analysis using qualitative reverse transcription polymerase chain reaction with two different sets of primers revealed the presence of ETV6-RUNX1 (short type) transcripts. Based on these data a diagnosis of ETV6-RUNX1-positive B-cell precursor ALL was made and treatment was initiated according to the ALL-IC BFM 2009 protocol. At day 33 a complete hematological remission was registered with a minimal residual disease of 0,003% detected by flow cytometry. ETV6-RUNX1 transcripts gradually decreases up to undetectable levels. Currently, our patients is still in complete hematological and molecular remission 2 years after treatment discontinuation.
Conclusion
In this study we report on a t(4;9)(q21;p24) in a male adolescent patient with B-ALL, also positive for the short type of ETV6-RUNX1 transcipts. The presence of this rare additional abnormality, that is recurrent for another hematological malignancy, was not associated with specific clinical, morphological or immunophenotypic features and it did not affect the characteristic favorable prognosis associated with ETV6-RUNX1.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, ETV6, prognosis
Abstract: PB1614
Type: Publication Only
Background
The cryptic translocation t(12;21)(p13;q22) and the respective ETV6-RUNX1 fusion gene, is the most common genetic abnormality in childhood acute lymphoblastic leukemia (ALL), accounting for 20%>25% of the cases, while it is a very rare finding in adolescents and adults with ALL, with an incidence of ≤1%. Additional chromosome abnormalities are detected in more than two thirds of cases, however the t(4;9)(q21;p24) has not been reported so far. This abnormality that results in the formation of SEC31A-JAK2 fusion gene has been previously reported as the first recurrent JAK2-associated translocation in classical Hodgkin lymphoma. To the best of our knowledge only two other cases of t(4;9)(q21;p24) have been reported so far – in a patient with ALL, with unknown ETV6-RUNX1 status and in a patient with undifferentiated lung carcinoma.
Aims
To present for the first time a rare case of t(4;9)(q21;p24) in an adolescent with a molecularly defined ETV6-RUNX1-positive B-ALL.
Methods
A 19-old male was admitted to the hospital because of pancytopenia and elevated serum lactate dehydrogenase levels, tested in relation to complaints of acute thoracic back pain.
Results
On admission, the physical exam was unremarkable. The initial laboratory tests revealed white blood cell counts of 1.6x109/l with no blasts; a hemoglobin level of 90 g/l and platelet counts of 10x109/l. On aspirate smear, the bone marrow was markedly hypercellular with a subtotal infiltration with lymphoblasts. Flow cytometry of bone marrow detected a blast cells population accounting for 48.3% of all cells with the following phenotype: Syto41+/CD45dim+/CD19+/CD10+/ CD20-/CD34+/CD38+/ CD58+. Conventional cytogenetic analysis demonstrated an abnormal karyotype: 45,XY,-4, der(9)t(4;9)(q21;p24),14ps+[5]/46,XY,14ps+[15], while molecular analysis using qualitative reverse transcription polymerase chain reaction with two different sets of primers revealed the presence of ETV6-RUNX1 (short type) transcripts. Based on these data a diagnosis of ETV6-RUNX1-positive B-cell precursor ALL was made and treatment was initiated according to the ALL-IC BFM 2009 protocol. At day 33 a complete hematological remission was registered with a minimal residual disease of 0,003% detected by flow cytometry. ETV6-RUNX1 transcripts gradually decreases up to undetectable levels. Currently, our patients is still in complete hematological and molecular remission 2 years after treatment discontinuation.
Conclusion
In this study we report on a t(4;9)(q21;p24) in a male adolescent patient with B-ALL, also positive for the short type of ETV6-RUNX1 transcipts. The presence of this rare additional abnormality, that is recurrent for another hematological malignancy, was not associated with specific clinical, morphological or immunophenotypic features and it did not affect the characteristic favorable prognosis associated with ETV6-RUNX1.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, ETV6, prognosis