Clinical Pathology
Contributions
Type: Publication Only
Background
Acute myeloid leukemia (AML) is a heterogeneous disorder with treatment results much inferior to acute lymphoblastic leukemia. Treatment failure is largely attributed to the persistence of leukemia stem cells (LSCs) which are less accessible and hence less responsive to chemotherapeutics. The classical LSC phenotype is CD34+/CD38-; however LSCs express other markers especially CD123 and CD133 which may be even earlier than CD34. We hypothesized that CD123 and CD133 may be better markers of LSCs and that higher frequency of LSCs at diagnosis may be associated with shorter survival.
Aims
To evaluate CD123 and CD133 as LSC markers as compared to the standard CD34+/CD38- and to study the impact of LSCs frequency at diagnosis on overall survival (OS) and disease free survival (DFS) in adult AML as well as correlate the LCS frequency with other findings at diagnosis.
Methods
The study was performed on 84 newly diagnosed AML patients including 51 Males and 33 females with an age range of 18 - 70 with a median of 31.5 years. Two 4 color panels of monoclonal antibodies were used: CD45/CD34/CD38/Cd123 and CD45/CD133/CD90/Cd33 and analyzed on Navios Coulter Flow Cytometer. Cell populations with different surface markers were calculated using the prism function of the soft ware. Results were correlated to other parameters at diagnosis. The median value for each marker alone and in different combinations (panels) was used to divide the cohort into high and low expressers. Patients were treated by (3+7) protocol; they were followed up for a period of 0.2-24 with a median of 5.5 months and evaluated for OS and DFS.
The study was performed according to the guidelines of Helsinki declaration for studies performed on human beings and approved by the Institution Review Board (IRB) of the National Cancer Institute, Cairo University. An informed signed consent was obtained from all study subjects before enrollment.
Results
Single markers or panels expression were not correlated to age, gender, percentage PB or BM blasts, Hb level, TLC or platelet count.
Among the studied single markers CD123 and CD133 high expression was associated with shorter OS (p= <0.001 and < 0.006 respectively) and DFS (p=<0.001). Among the panels, CD123+/CD34+/CD38- was the best discriminator for OS (p=0.005) followed by CD123+/CD34- /CD38+ (p=0.025) and CD34+/CD38- (p=0.025). For DFS CD123+/CD34+/CD38- and CD123+/CD34-/CD38+ were both associated with shorter DFS (p=<0.001); CD34+/CD38- population level at diagnosis had no significant impact on DFS.
Summary
The classical phenotype of CD34+/CD38- is not inclusive; LSC may be present among CD34- and/or CD38+ populations. CD123 and CD133 are sensitive markers, even better than CD34+/CD38-, for the detection of LSC. Higher frequency of leukemia stem cells at diagnosis is associated with shorter OS and DFS.
Keyword(s): Acute myeloid leukemia, CD133+, Leukemic stem cell
Session topic: Publication Only
Type: Publication Only
Background
Acute myeloid leukemia (AML) is a heterogeneous disorder with treatment results much inferior to acute lymphoblastic leukemia. Treatment failure is largely attributed to the persistence of leukemia stem cells (LSCs) which are less accessible and hence less responsive to chemotherapeutics. The classical LSC phenotype is CD34+/CD38-; however LSCs express other markers especially CD123 and CD133 which may be even earlier than CD34. We hypothesized that CD123 and CD133 may be better markers of LSCs and that higher frequency of LSCs at diagnosis may be associated with shorter survival.
Aims
To evaluate CD123 and CD133 as LSC markers as compared to the standard CD34+/CD38- and to study the impact of LSCs frequency at diagnosis on overall survival (OS) and disease free survival (DFS) in adult AML as well as correlate the LCS frequency with other findings at diagnosis.
Methods
The study was performed on 84 newly diagnosed AML patients including 51 Males and 33 females with an age range of 18 - 70 with a median of 31.5 years. Two 4 color panels of monoclonal antibodies were used: CD45/CD34/CD38/Cd123 and CD45/CD133/CD90/Cd33 and analyzed on Navios Coulter Flow Cytometer. Cell populations with different surface markers were calculated using the prism function of the soft ware. Results were correlated to other parameters at diagnosis. The median value for each marker alone and in different combinations (panels) was used to divide the cohort into high and low expressers. Patients were treated by (3+7) protocol; they were followed up for a period of 0.2-24 with a median of 5.5 months and evaluated for OS and DFS.
The study was performed according to the guidelines of Helsinki declaration for studies performed on human beings and approved by the Institution Review Board (IRB) of the National Cancer Institute, Cairo University. An informed signed consent was obtained from all study subjects before enrollment.
Results
Single markers or panels expression were not correlated to age, gender, percentage PB or BM blasts, Hb level, TLC or platelet count.
Among the studied single markers CD123 and CD133 high expression was associated with shorter OS (p= <0.001 and < 0.006 respectively) and DFS (p=<0.001). Among the panels, CD123+/CD34+/CD38- was the best discriminator for OS (p=0.005) followed by CD123+/CD34- /CD38+ (p=0.025) and CD34+/CD38- (p=0.025). For DFS CD123+/CD34+/CD38- and CD123+/CD34-/CD38+ were both associated with shorter DFS (p=<0.001); CD34+/CD38- population level at diagnosis had no significant impact on DFS.
Summary
The classical phenotype of CD34+/CD38- is not inclusive; LSC may be present among CD34- and/or CD38+ populations. CD123 and CD133 are sensitive markers, even better than CD34+/CD38-, for the detection of LSC. Higher frequency of leukemia stem cells at diagnosis is associated with shorter OS and DFS.
Keyword(s): Acute myeloid leukemia, CD133+, Leukemic stem cell
Session topic: Publication Only