Stem Cells International

Review Article

Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia

Table 1

LIC activity in prospectively isolated subpopulations in ALL.
LIC markerALL entityTransplanted cells EngraftmentAdministration route
and
mouse strain		Reference
CD34+ CD38−Adult Ph+ ALL2 × 104YesIV 
NOD/SCID		[60]
CD34+ CD10+ 
CD34+ CD10− 
CD34− CD10+ 
CD34− CD10− 
CD34+ CD19+ 
CD34+ CD19− 
CD34− CD19+ 
CD34− CD19−		Adult and infant Ph− Pre-B and cALL1 × 105–1 × 107
7 × 104–3 × 106
1 × 105–1 × 106
1 × 105–1 × 107
1 × 105–1 × 107
5 × 104–2 × 105
1 × 105–1 × 106
1 × 105–1 × 106		No 
Yes 
No 
No 
No 
Yes 
No 
No		IV 
NOD/SCID		[61]
CD34+ CD38− CD19+Infant Ph+ and ETV6/Runx1+ ALL5.5 × 105YesIV 
NOD/SCID/B2m−/−		[59]
CD34+ CD38low CD19+ 
CD34+ CD38+ CD19+		Infant ETV6/Runx1+ ALL5 × 104–3.5 × 105
1 × 106–2.2 × 106		Yes 
No		IV/IF 
NOD/SCID		[63]
CD34+ CD19− 
CD34+ CD19+ 
CD34− CD19+ 
CD19+ CD20−low
CD19+ CD20+high		Infant B-ALL2 × 103
2 × 103
2 × 103
2 × 103
2 × 103		Yes 
Yes 
Yes 
Yes 
Yes		IF 
NOD/SCID and NSG		[65]
CD34+ CD38+ CD19+ 
CD34+ CD38− CD19+ 
CD34+ CD38− CD10− CD19−		Infant B-ALL5 × 103–5 × 105
5 × 105–1 × 105
2 × 103		Yes 
Yes 
Hematopoietic engraftment		IV 
NSG		[64]
CD133+ CD19+ 
CD133+ CD19− 
CD133− CD19+ 
CD133− CD19− 
CD34+ CD19− 
CD133+ CD38+ 
CD133+ CD38−		Infant B-ALL1 × 104–1 × 106
1 × 10³ 
1 × 105–1 × 107
1 × 105–1 × 106
1 × 105
1 × 103–1 × 105
1 × 102		No 
Yes 
No 
No 
Yes 
No 
Yes		IV 
NOD/SCID		[132]
CD9+ 
CD9−		Pre-B-ALL cell lines2 × 104–1 × 106
1 × 106		Yes 
No		IV 
NOG		[133]
CD34+ CD38− CD19+ 
CD34+ CD38+ CD19+ 
CD34− CD38+ CD19+		Adult Ph+ ALL and CML BP5 × 103–1 × 104
5 × 103–1 × 104
5 × 103–1 × 104		Yes 
Yes 
No		IV 
NOD/SCID and NOG		[134]
CD10 low/high 
CD20 low/high 
CD34 low/high		Ph+/− B-ALL1 × 102–1 × 103
1 × 102–1 × 103
1 × 102–1 × 103		Yes 
Yes 
Yes		IF 
NSG		[135]
CD34+ CD38+ CD19+ CD33+ 
CD34− CD38+ CD19+ CD33+ 
CD34− CD38+ CD19+ CD33− 
CD34+ CD38+ CD19+ 
CD34− CD19+ 
CD34+ CD38− CD19− CD33− 
CD34+ CD38− CD19− CD33+		Infant MLL+ ALL1 × 103
1 × 103
1 × 103
1 × 103
1 × 103
1 × 103
1 × 103		Yes 
Yes 
Yes 
Yes 
Yes 
Hematopoietic engraftment 
Yes		IV 
NSG		[67]
CD34+ CD19+ NG2− 
CD34+ CD19+ NG2+ 
CD34− CD19+ NG2− 
CD34− CD19+ NG2+ 
CD34− CD19− 
CD34+ CD19−		Infant MLL+ ALL2 × 103–1 × 106
1 × 104–1 × 106
1 × 103–1 × 105
1 × 104–1.5 × 105
1 × 103–1 × 105
5 × 103–5 × 104		Yes 
Yes 
Yes 
Yes 
No 
Yes		IV 
NOD/SCID and NSG		[105]
CD34+ CD38− CD58− 
CD34+ CD38− CD58+ 
CD34+ CD38+ CD58− 
CD34+ CD38+ CD58+		Ph+ ALL1 × 103–1 × 105
1 × 103–1 × 107
1 × 103–1 × 107
1 × 103–1 × 107		Yes 
No 
No 
No		IF 
NOD/SCID 
(anti CD122 conditioned)		[68]
CD34+ CD38+ CD19+ 
CD34+ CD38−/low CD19+		Pro-B-ALL2 × 103–2 × 106YesIF
NSG		[104]
Ph: Philadelphia chromosome; NG2: neural/glial antigen 2; IV: intravenous; IF: intrafemoral; NSG: NOD/SCID gamma.