Evidence for Early Hematopoietic Progenitor Cell Involvement in Acute Promyelocytic Leukemia

CD34‐positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform

“…Recent utilization of molecular testing has led to the identification of PML-RAR␣ positive variants with atypical morphology [15,33]. Although expression of CD34 was initially considered uncommon [14], recent studies have shown that CD34 positivity occurs in about 20-30% of newly diagnosed cases [12,[20][21][22]. The significance of CD34 expression in APL is unknown but likely identifies an immature form of APL.…”

“…Until recently, the detection of CD34 in t(15;17) APL was considered infrequent [14]; however, several reports have now shown that expression of CD34 occurs in a significant proportion of newly diagnosed t(15;17) APL patients [12,[20][21][22]. Although CD34 positivity has been associated with a lower rate of complete remission in combined subtypes of acute myeloid leukemia (AML) [23][24][25], the significance of CD34 expression in t(15;17)/ PML-RAR␣ APL is not known.…”

Acute promyelocytic leukemia: where does it stem from?

“…50 These data provide further support for the 'lineage promiscuity' hypothesis, whereby the immunophenotype of leukemic blasts is largely a reflection of their cell of origin. Indeed, Edwards et al 51 have demonstrated the presence of the PML-RARA fusion by fluorescence in situ hybridization (FISH) within the majority of cells residing within the CD34 þ CD38À fraction in two cases of CD2-positive hypogranular variant APL. Taken together, these data suggest that a significant proportion of APL cases arise in more primitive progenitors than previously considered to be the case.…”

Concepts of human leukemic development

“…In support of the view that APL may originate from committed progenitors rather than stem cells, a frequently cited study reported that PML-RARa transcripts could be detected in CD34 þ CD38 þ but not CD34 þ CD38 -cells by RT-PCR, suggesting that primitive hematopoietic cells are not involved in the leukemic process in APL (Turhan et al, 1995). However, a more recent study using FISH demonstrated that the PML-RARa fusion gene was present in the majority of CD34 þ CD38 À cells (Edwards et al, 1999), suggesting that transcription of PML-RARa is suppressed in CD34 þ CD38 -cells and providing evidence that at least in some cases APL arises in primitive cells. This is further supported by recent data that the T-lineage-affiliated CD2 locus lies within an open chromatin domain in primary APL blasts regardless of the surface expression of CD2 (Grimwade et al, 2002), suggesting that the cell of origin is a primitive multipotential cell (see lineage promiscuity, above).…”