Vercauteren Sm, Zapf R, Sutherland Hj
Terry Fox Laboratory, British Columbia Cancer Agency, Division of Hematology and Hematopathology, Vancouver General Hospital, Vancouver, Canada.
Cytotherapy. 2007;9(2):194-204. doi: 10.1080/14653240601164042.
AML blast populations are heterogeneous in their phenotype and functional properties, and contain a small subset of cells that regenerate leukemia in immunocompromised mice or produce clonogenic progeny in long-term cultures. This suggests the existence of a hierarchy of AML progenitor cells. CD33 is a myeloid marker absent on normal hematopoietic stem cells but expressed in about 75% of AML patients, and has been used for BM purging strategies and Ab-targeted therapies. These CD33 Ab therapies benefit only a minority of AML patients, suggesting that AML stem cells are heterogeneous in their CD33 expression.
In order to evaluate this question, we determined expression levels of CD34 and CD33 on AML progenitors with long-term in vitro proliferative ability and NOD/SCID engrafting ability.
The CD34(+) CD33(-) subfraction contained the majority of progenitors detected in vitro and most often engrafted the mice. This proliferation was leukemic from the CD34(+) AML patients, however from the CD34(-) AML patients only normal progenitors were detected in this fraction in some cases.
These data suggest that most leukemic progenitors of CD34(+) patients do not express CD33. In contrast, CD34(-) AML primitive leukemic progenitors may be CD33(+). CD34(-) AML patients could potentially benefit most from CD33-targeted therapies or purging.
急性髓系白血病（AML）原始细胞群体在表型和功能特性上具有异质性，并且包含一小部分细胞，这些细胞可在免疫缺陷小鼠中使白血病再生，或在长期培养中产生克隆性后代。这提示AML祖细胞存在层级结构。CD33是一种髓系标志物，在正常造血干细胞上不存在，但在约75%的AML患者中表达，并且已被用于骨髓净化策略和抗体靶向治疗。这些CD33抗体疗法仅使少数AML患者受益，提示AML干细胞在CD33表达上具有异质性。
为了评估这个问题，我们测定了具有长期体外增殖能力和NOD/SCID植入能力的AML祖细胞上CD34和CD33的表达水平。
CD34(+)CD33(-)亚群包含了体外检测到的大多数祖细胞，并且最常植入小鼠体内。这种增殖来自CD34(+)AML患者的白血病细胞，然而在某些情况下，对于CD34(-)AML患者，在这个亚群中仅检测到正常祖细胞。
这些数据提示，大多数CD34(+)患者的白血病祖细胞不表达CD33。相比之下，CD34(-)AML原始白血病祖细胞可能是CD33(+)。CD34(-)AML患者可能最能从CD33靶向治疗或净化中获益。
