Immunophenotype in Chronic Myelomonocytic Leukemia: Is It Closer to Myelodysplastic Syndromes or to Myeloproliferative Disorders?.

Abstract

Chronic myelomonocytic leukaemia (CMML) is an entity with a heterogeneous clinical evolution, initially included among myelodysplastic syndromes (MDS) according to the FAB classification. The recent WHO classification brings CMML closer to myeloproliferative disorders, and moved it into a new category termed myelodysplastic/myeloproliferative diseases (MDS/MPD). Aim: To describe the immunophenotypic profile of CMML and to compare it with the phenotype described in MDS and MPD. Patients: 76 patients: 20 CMML (15 CMML I, 5 CMML II), 38 MDS (refractory cytopenia with multilineage dysplasia), and 18 MPD (11 essential thrombocytemia, 2 chronic idiopathic myelofibrosis, and 5 polycythemia vera). Material and Methods: Flow cytometry immunophenotyping (FCI) in bone marrow samples. Data studied: 1 In the myeloid lineage: abnormalities in granularity and CD45 distribution, abnormalities in the phenotypic pattern of myeloid development (CD16/CD11b/CD13), and the absence of CD10 expression on mature granulocytes (CD10−). 2 In the monocytic lineage: CD2 and CD56 expression. 3 In the red cells: abnormalities in CD71 and glycophorin A distribution. 4 In B-cells, detection of a low percentage of CD10+ B-cell precursors (less than 1% of bone marrow B-cells). 5 In myeloblasts, identification of more than >5% CD34+ cells, and evaluation of aberrant expression of CD7 and TdT in these cells (positive expression was described when >10% of CD34+ cells were positive for any of these antigens). Results: Abnormal cases among those studied for each parameter analysed is specified in the table. Patients with CMML and MDS showed statistically significant differences (p<0.05) in their B-cell development and CD56 monocyte expression. Significant differences between CMML and MPD were found in CD45 myeloid distribution, myeloid antigenic profile, CD56 and CD2 monocyte expression and B-cell development. Immunophenotypic data in patients with MDS (row1), CMML (row2), and MPD (row3). Abnormal SSC/CD45 Abnormal myeloid CD16/CD11b/CD13 CD10− neutrophils CD2+ monocytes CD56+ monocytes Abnormal erythroid CD71/GlyA <1% CD10+ B cells >5% CD34+ MDS: myelodysplastic syndromes; CMML: chronic myelomonocytic leukemia; MPD: myeloproliferative disorders. 33/38 35/38 15/30 5/27 5/31 27/38 16/31 2/38 20/20 20/20 4/17 8/17 9/16 16/19 14/17 0/20 4/18 5/18 1/18 1/18 0/16 12/17 4/18 0/18 Conclusions: With the number of cases studied, higher similarities can be found between CMML and MDS immunophenotypic profiles. The antibody panel selected, including several abnormalities previously described in patients with MDS, might justify the differences found between CMML and MPD. However, it does not explain the relationship between the immunophenotypic profile of CMML and MDS. Abnormalities in B-cell development and aberrant expression of CD56 on monocytes were the most useful data to distinguish CMML and MPD. Although the number of patients studied is still low, quantification of CD34+ cells did not help to identify CMML with an aggressive clinical course.

Flow cytometry immunophenotypic findings in chronic myelomonocytic leukemia and its utility in monitoring treatment response

“…Immunophenotypic assessment of monocytes, on the other hand, revealed alterations in most (96%) CMML cases in our study with frequently decreased CD45 and HLA‐DR, altered CD64 and CD14, and aberrant expression of CD2 and CD56. These changes are similar to what was reported previously . Increased expression of CD56 on monocytes has been reported in the peripheral blood of healthy individuals and reactive BM samples from patients who had received chemotherapy for leukemia .…”

“…Indeed, CMML shares with MDS clinical and biologic similarity, and it was considered as a form of MDS by the French–American–British (FAB) classification . Immunophenotypically, CMML also has been shown to be closer to MDS than MPN . Interestingly, increased expression of mature myelomonocytic markers in CD34 + myeloblasts, including CD64, CD15, and rarely, CD11b, was only observed in a small subset of CMML patients (20 of 118, 17%), similar to what we observed in MDS patients .…”

“…A decrease in stage I hematogones was observed in over 90% of CMML patients indicating that, similar to MDS , the CD34 + cells in CMML are markedly myeloid‐biased, and the generation of B‐lymphoid progeny is severely impaired. This is in contrast to MPN in which stage I hematogones are more frequently preserved . Indeed, CMML shares with MDS clinical and biologic similarity, and it was considered as a form of MDS by the French–American–British (FAB) classification .…”

“…In contrast, there has been much less emphasis on using FCI in CMML patients. In the relatively few studies in the literature , most studies included only a small number of CMML patients and markers, and analysis was focused predominantly on the monocyte population. Although a number of immunophenotypic changes in monocytes have been described, it is uncertain if these changes are unique to CMML.…”

Recent advances in diagnosis, molecular pathology and therapy of chronic myelomonocytic leukaemia

“…Nevertheless, some significant differences were determined between the antigen expression patterns of monocytic AML and CMML, respectively. Subira et al (2008) reported aberrant CD2 expression in 47% of CMML cases and Gorczyca (2004) documented aberrant CD2 expression in 34% of CMML cases but only in 14% of AML FAB M5 cases. According to Xu et al (2005), aberrant co-expression of CD56 combined with underexpression of a myeloid marker (e.g.…”