A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication.
In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AML-cuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AML-cuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.
Kussick
S J
SJ
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. skussick@u.washington.edu <skussick@u.washington.edu>
Stirewalt
D L
DL
Yi
H S
HS
Sheets
K M
KM
Pogosova-Agadjanyan
E
E
Braswell
S
S
Norwood
T H
TH
Radich
J P
JP
Wood
B L
BL
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D020440:Gene Duplication; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D019089:Stem Cell Factor; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3
D006684:HLA-DR Antigens; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3