Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34).
BACKGROUND
The t(6;9)(p23;q34);DEK-NUP214 [t(6;9)] abnormality is found in 0.7-1.8% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FLT3-ITD mutations are detected in t(6;9) patients. The t(6;9) abnormality is associated with poor outcomes. We studied the clinicopathologic and molecular profiles of patients with AML/MDS carrying t(6;9).


METHODS
We collected clinical data of nine patients with AML/MDS with isolated t(6;9) (median age = 41 years; male/female = 4/5) and genotyped DNAs using whole exome, Sanger, and targeted sequencing.


RESULTS
Our cohort was characterized by frequent multilineage dysplasia (56%), absence of phospho-STAT3/STAT5 expression, presence of myeloid markers (CD13, CD33, CD34, CD117, HLA-DR) with an aberrant expression of CD7, and poor outcome (median survival of 20 months). Although basophilia has been described in association with t(6;9), we observed lack of marrow basophilia in our cohort. Molecularly, 83% (5/6) of patients with AML/MDS with t(6;9) were characterized by at least one somatic mutation. Among them, four patients showed multiple mutations. FLT3-ITD mutations were detected in 33% of patients (2/6); 80% (4/5) of mutant patients died even after hematopoietic stem cell transplantation.


CONCLUSIONS
Our data demonstrated that AML/MDS patients with t(6;9) have diverse molecular mutations regardless of the presence of FLT3 mutations, which may contribute to their poor survival outcomes.
Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
V
http://orcid.org/0000-0002-2993-1509
V
Visconte
Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
S
S
Shetty
Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
B
B
Przychodzen
Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
C
C
Hirsch
Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
J
J
Bodo
Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
J P
JP
Maciejewski
Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
E D
http://orcid.org/0000-0001-8623-4067
ED
Hsi
Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
H J
HJ
Rogers
D000328:Adult; D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D059472:Exome; D005260:Female; D020440:Gene Duplication; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D012189:Retrospective Studies; D020080:Tandem Repeat Sequences; D014178:Translocation, Genetic; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D051941:fms-Like Tyrosine Kinase 3

AML
; 
MDS
; t(6;9)(p23;q34)