Contributions
Abstract: PB1664
Type: Publication Only
Background
Overlapping features often hamper the differential diagnosis of chronic myelomonocytic leukemia (CMML) vs. acute monoblastic/monocytic leukemias (AMML).
Aims
We investigated the proliferation index (PI) of different bone marrow (BM) cell subsets by multiparameter flow cytometry as potentially useful for discrimination of both disease entities.
Methods
The PI (percentage of cycling S+G2/M cells) was studied using a 4-color (CD34/CD45/CD11b/CD13) antibody panel that included the DRAQ5 DNA stain. Thus, a total of 145 BM samples corresponding to healthy subjects (NBM; n=67), CMML (n=31; CMML-1, n=25 and CMML-2, n=6) and AMML (n=47; monoblastic leukemia, n=38 and monocytic leukemia, n=9) were studied for the PI among the more immature BM cell component in each case (i.e. CD34+ cells and/or leukemic cells) and also (residual) monocytic, neutrophil and erythroid lineage cells.
Results
As expected in NBN, the highest PI was shown by erythroid cells, followed by CD34+ hematopoietic precursors, neutrophil and monocytic cells (PI of 28%, 15%, 5% and 4%, respectively).
Conversely, the analysis of the more immature BM cell component from monocytic leukemias revealed that CD34+ cells from CMML patients had normal proliferation rates (PI of 16% vs. 15% in NBM), while significantly decreasing in AMML (CD34+) leukemic cells (7% vs. 15%; p<0.001). In detail, the PI of CD34+ cells from CMML-1 was significantly higher vs. (CD34+) leukemic cells from monoblastic and monocytic leukemias (PI of 17% vs. 7% and 4%, respectively; p<0.001), while a similar PI was found among CD34+ cells from CMML-2 vs. leukemic cells from both groups of AMML patients (PI of 3%; p>0.05). As noted, a tendency to a lower PI of the (CD34+) blast cell compartment is observed from monoblastic to monocytic leukemia (7% vs. 4%, respectively; p>0.05).
In turn, AMML monocytic-lineage leukemic cells depicted a significantly increased proliferation vs. monocytic cells from both NBM and CMML (PI of 7% vs. 4% and 3%, respectively; p=0.001). Such overall increased PI was mostly related to the enhanced proliferation of monoblastic leukemia cells, which was almost twice the PI of monocytic cells from all the other groups (PI of 7% vs. 3%, 3% and 4% for LMMC1, LMMC2 and monocytic leukemia, respectively; p=0.001).
Most strikingly, the proliferation of the erythroid-lineage cells was found significantly decreased in AMML, as compared to NBM (PI of 25% vs. 28%: p=0.02). Interestingly, this was at the expense of erythroid cells from monocytic leukemia, which showed a significantly lower proliferation vs. all the other groups (PI:15% vs. 27%, 30% and 23% for monoblastic leukemia, CMML-1 and CMML-2, respectively; p=0.005). No differences were found in the PI of any other residual cell lineage investigated.
Conclusion
The detection of decreased levels of proliferation, particularly among erythroid cells might help the differential diagnosis of CMML-2 vs. monocytic leukemia, whereas an enhanced proliferation of leukemic cells is particularly recurrent in monoblastic leukemia vs. the other monocytic lineage leukemias investigated.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Leukemia, monocyte, Proliferation
Abstract: PB1664
Type: Publication Only
Background
Overlapping features often hamper the differential diagnosis of chronic myelomonocytic leukemia (CMML) vs. acute monoblastic/monocytic leukemias (AMML).
Aims
We investigated the proliferation index (PI) of different bone marrow (BM) cell subsets by multiparameter flow cytometry as potentially useful for discrimination of both disease entities.
Methods
The PI (percentage of cycling S+G2/M cells) was studied using a 4-color (CD34/CD45/CD11b/CD13) antibody panel that included the DRAQ5 DNA stain. Thus, a total of 145 BM samples corresponding to healthy subjects (NBM; n=67), CMML (n=31; CMML-1, n=25 and CMML-2, n=6) and AMML (n=47; monoblastic leukemia, n=38 and monocytic leukemia, n=9) were studied for the PI among the more immature BM cell component in each case (i.e. CD34+ cells and/or leukemic cells) and also (residual) monocytic, neutrophil and erythroid lineage cells.
Results
As expected in NBN, the highest PI was shown by erythroid cells, followed by CD34+ hematopoietic precursors, neutrophil and monocytic cells (PI of 28%, 15%, 5% and 4%, respectively).
Conversely, the analysis of the more immature BM cell component from monocytic leukemias revealed that CD34+ cells from CMML patients had normal proliferation rates (PI of 16% vs. 15% in NBM), while significantly decreasing in AMML (CD34+) leukemic cells (7% vs. 15%; p<0.001). In detail, the PI of CD34+ cells from CMML-1 was significantly higher vs. (CD34+) leukemic cells from monoblastic and monocytic leukemias (PI of 17% vs. 7% and 4%, respectively; p<0.001), while a similar PI was found among CD34+ cells from CMML-2 vs. leukemic cells from both groups of AMML patients (PI of 3%; p>0.05). As noted, a tendency to a lower PI of the (CD34+) blast cell compartment is observed from monoblastic to monocytic leukemia (7% vs. 4%, respectively; p>0.05).
In turn, AMML monocytic-lineage leukemic cells depicted a significantly increased proliferation vs. monocytic cells from both NBM and CMML (PI of 7% vs. 4% and 3%, respectively; p=0.001). Such overall increased PI was mostly related to the enhanced proliferation of monoblastic leukemia cells, which was almost twice the PI of monocytic cells from all the other groups (PI of 7% vs. 3%, 3% and 4% for LMMC1, LMMC2 and monocytic leukemia, respectively; p=0.001).
Most strikingly, the proliferation of the erythroid-lineage cells was found significantly decreased in AMML, as compared to NBM (PI of 25% vs. 28%: p=0.02). Interestingly, this was at the expense of erythroid cells from monocytic leukemia, which showed a significantly lower proliferation vs. all the other groups (PI:15% vs. 27%, 30% and 23% for monoblastic leukemia, CMML-1 and CMML-2, respectively; p=0.005). No differences were found in the PI of any other residual cell lineage investigated.
Conclusion
The detection of decreased levels of proliferation, particularly among erythroid cells might help the differential diagnosis of CMML-2 vs. monocytic leukemia, whereas an enhanced proliferation of leukemic cells is particularly recurrent in monoblastic leukemia vs. the other monocytic lineage leukemias investigated.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Leukemia, monocyte, Proliferation