Contributions
Abstract: PB1421
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Translocation t(6;9)(p22;q34) is a recurrent rare genetic abnormality which defines an unique acute myeloid leukemia (AML) subtype characterized by poor prognosis. At molecular level, t(6;9) results in DEK-NUP214 fusion gene formation which has a key role in the pathogenesis of the disease. The translocation accounts for only 0.5-2% of AML cases and therefore information concerning the clinical and laboratory features of t(6;9)/DEK-NUP214-positive patients (pts) is relatively limited. No data concerning the incidence and characteristics of AML with this abnormality in Bulgarian patients have been published so far.
Aims
To determine the incidence and the main characteristics of Bulgarian patients with t(6;9)/DEK-NUP214-positive AML.
Methods
Bone marrow aspirates of 945 consecutive adult pts with confirmed diagnosis AML were tested centrally in the Laboratory of Cytogenetics and Molecular Biology of the National Specialized Hospital for Active Treatment of Hematological Diseases – Sofia. Successful karyotypes were obtained in 812 of the cases. In all pts with cytogenetically detected t(6;9), the presence of the DEK-NUP214 fusion transcripts was confirmed by reverse transcription polymerase chain reaction (RT-PCR). AML diagnosis and subclassification were performed according to the WHO Classification criteria (2016).
Results
Overall, t(6;9)/DEK-NUP214 was detected in 6 (0.74%) pts, including 4 males and 2 females, with a mean age of 40±7.4 years (range 33 – 53 years). The median white blood cell (WBC) count in positive pts was 86x109/L (range 21-106x109/L), the median platelet count - 29x109/L (range 14-97x109/L), and the median hemoglobin level - 78.5 g/L (range 55-96 g/L). All pts were with de novo AML. The average bone marrow blast cell infiltration was 62.7%±29.5%. In 5/6 pts morphology revealed a monocytic component and AML was classified as AML-M4 according to FAB criteria. However, basophilia wasn’t encountered in any of the cases. In 5 patients, t(6;9) was the sole chromosome abnormality, while in 1 patient, in addition, trisomy 13 was observed in all metaphases. FLT3-ITD was found in 3/6 of the DEK-NUP214-positive pts, and interestingly, a certain number of “cup-like” blasts was seen in all of them. Immunophenotyping revealed CD34 and/or CD117 positivity and aberrant myelomonocytic phenotypes in all pts, with an aberrant expression of CD56 in 2 of them. In two pts early dead occurred. In the remaining 4 pts, a standard 7+3 induction protocol ± midostaurin was initiated, but without significant reduction of blast population. Complete remission (CR) was achieved in 2 pts after a second high-dose induction course, followed by allogenic stem cell transplantation in 1 of them who is still alive 30 months after the diagnosis. The other was lost of follow up. The remaining patients were refractory and died within 2-13 months.
Conclusion
The present study confirmed the low incidence of t(6;9)/DEK-NUP214 in Bulgarian pts with AML. Despite of the heterogeneous clinical and laboratory features, our series was characterized by relatively younger age, high WBC counts, myelomonocytic morphology, absence of additional chromosomal aberrations in most of the cases, presence of FLT3-ITD in half of the pts and poor outcome with conventional chemotherapy.
Keyword(s): AML, Molecular markers, Translocation
Abstract: PB1421
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Translocation t(6;9)(p22;q34) is a recurrent rare genetic abnormality which defines an unique acute myeloid leukemia (AML) subtype characterized by poor prognosis. At molecular level, t(6;9) results in DEK-NUP214 fusion gene formation which has a key role in the pathogenesis of the disease. The translocation accounts for only 0.5-2% of AML cases and therefore information concerning the clinical and laboratory features of t(6;9)/DEK-NUP214-positive patients (pts) is relatively limited. No data concerning the incidence and characteristics of AML with this abnormality in Bulgarian patients have been published so far.
Aims
To determine the incidence and the main characteristics of Bulgarian patients with t(6;9)/DEK-NUP214-positive AML.
Methods
Bone marrow aspirates of 945 consecutive adult pts with confirmed diagnosis AML were tested centrally in the Laboratory of Cytogenetics and Molecular Biology of the National Specialized Hospital for Active Treatment of Hematological Diseases – Sofia. Successful karyotypes were obtained in 812 of the cases. In all pts with cytogenetically detected t(6;9), the presence of the DEK-NUP214 fusion transcripts was confirmed by reverse transcription polymerase chain reaction (RT-PCR). AML diagnosis and subclassification were performed according to the WHO Classification criteria (2016).
Results
Overall, t(6;9)/DEK-NUP214 was detected in 6 (0.74%) pts, including 4 males and 2 females, with a mean age of 40±7.4 years (range 33 – 53 years). The median white blood cell (WBC) count in positive pts was 86x109/L (range 21-106x109/L), the median platelet count - 29x109/L (range 14-97x109/L), and the median hemoglobin level - 78.5 g/L (range 55-96 g/L). All pts were with de novo AML. The average bone marrow blast cell infiltration was 62.7%±29.5%. In 5/6 pts morphology revealed a monocytic component and AML was classified as AML-M4 according to FAB criteria. However, basophilia wasn’t encountered in any of the cases. In 5 patients, t(6;9) was the sole chromosome abnormality, while in 1 patient, in addition, trisomy 13 was observed in all metaphases. FLT3-ITD was found in 3/6 of the DEK-NUP214-positive pts, and interestingly, a certain number of “cup-like” blasts was seen in all of them. Immunophenotyping revealed CD34 and/or CD117 positivity and aberrant myelomonocytic phenotypes in all pts, with an aberrant expression of CD56 in 2 of them. In two pts early dead occurred. In the remaining 4 pts, a standard 7+3 induction protocol ± midostaurin was initiated, but without significant reduction of blast population. Complete remission (CR) was achieved in 2 pts after a second high-dose induction course, followed by allogenic stem cell transplantation in 1 of them who is still alive 30 months after the diagnosis. The other was lost of follow up. The remaining patients were refractory and died within 2-13 months.
Conclusion
The present study confirmed the low incidence of t(6;9)/DEK-NUP214 in Bulgarian pts with AML. Despite of the heterogeneous clinical and laboratory features, our series was characterized by relatively younger age, high WBC counts, myelomonocytic morphology, absence of additional chromosomal aberrations in most of the cases, presence of FLT3-ITD in half of the pts and poor outcome with conventional chemotherapy.
Keyword(s): AML, Molecular markers, Translocation