CD34-positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform.
Acute promyelocytic leukemia (APL) has a favorable prognosis. Current therapy includes chemotherapy used in combination with all-trans-retinoic acid (ATRA). Although the differentiating effects of ATRA on promyelocytes have been well established, in vitro studies have shown that less-differentiated APL blasts (CD34(+)) demonstrate a variable responsiveness to ATRA. To assess the clinical relevance of this finding, we analyzed a cohort of 38 patients with t(15;17) and/or PML-RARalpha APL to determine the incidence and laboratory features of CD34(+) APL. Thirty-two percent (12/38) of cases were CD34(+). There was a difference in WBC at presentation between CD34(+) and CD34(-) cases (34.6 +/- 9.2, mean +/- standard error vs. 5.4 +/- 2.0, P = 0.009). Patients with CD34(+) APL demonstrated a micro/hypogranular phenotype (75%) (P = 0.001), co-expression of CD2(+) (83%) (P = 0.001), and the bcr3 isoform (100%) (P = 0.017). In contrast, CD34(-) cases demonstrated hypergranular morphology (65%), CD2(+) (15%), and the bcr1 isoform (50%). A high presenting WBC count (\G10 x 10(9)/L) was associated with an inferior overall survival (Log rank = 0.0047). Patients with CD34(+) APL demonstrated an incidence of early mortality of 50%. Despite a marked correlation between CD34 positivity and increased WBC count, overall survival of CD34(+) and CD34(-) cases did not differ significantly in our small cohort. Immunophenotypic analysis for CD34 expression should be included in future large APL trials to determine if detection of CD34(+) blasts represents an independent adverse prognostic factor.
Department of Laboratory Medicine, Hamilton Health Sciences Corporation, Hamilton, Canada.
R
R
Foley
P
P
Soamboonsrup
R F
RF
Carter
A
A
Benger
R
R
Meyer
I
I
Walker
Y
Y
Wan
W
W
Patterson
A
A
Orzel
L
L
Sunisloe
B
B
Leber
P B
PB
Neame
D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D018801:CD2 Antigens / Q000096:biosynthesis; D015331:Cohort Studies; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D007964:Leukocytosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D015513:Oncogene Proteins / Q000096:biosynthesis; D015514:Oncogene Proteins, Fusion; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D015996:Survival Rate; D014178:Translocation, Genetic
D018952:Antigens, CD34; D018801:CD2 Antigens; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr