Assem, M. M., Y. H. Elnahass, N. M. El Sharkawy, H. N. Raslan, F. A. Elrefaey, and Y. M. Elmeligui,
"Expression of the Chemokine MCP-1 and Chemokine Receptors CXCR4 and CCCR2 in Egyptian Acute Myeloid Leukemia Patients",
Life Science Journal, vol. 9, issue 4, pp. 4529-4535, 2012.
AbstractAbstract: Background: AML blasts of different FAB subsets express specific chemokines and chemokine receptors depending on their degree of maturation which might account for some aspects in their pattern of extramedullary invasion (EMI) and accumulation of leukemic cells. Objectives: We aimed to define the pattern of chemokine MCP- 1 and chemokine receptors CXCR4 and CCR2 expression by AML blasts in two AML FAB subgroups, myeloid M0/M1/ M2 and monocytic M4/M5 groups to determine their impact on tumor load and EMI. Patients and Methods: The study was performed on 50 de novo AML patients. Expression of CXCR4 and CCR2 was measured by flow cytometry while MCP-1 expression was detected by reverse transcriptase polymerase chain reaction (RTPCR). Results: Median TLC was 65.6 x 109 /L in MCP1 positive patients versus 37.2 x 109 /L in MCP1 negative cases (p = 0.07). MCP1 was positive in 14/20 (70%) patients with EMI versus 6/20 (30%) patients only without EMI (p = 0.05). CXCR4 was positive in most AML patients (38/50, 76%) with no significant difference between AML FAB subgroups (p =0.9). However, median CXCR4 percent positivity by flow cytometry was 79% (0.3-98) in the M4/M5 group versus 57.5% (1.9-89) in the M0/M1/ M2 (p = 0.08). CXCR4 was positive in 35/43 patients (81%) with hypercellular bone marrow (BM) at diagnosis (p =0.02). CCR2 positivity was higher in M4/M5 group (8/21, 38%) than M0/M1/M2 group (2/29, 7%) (p =0.006). Meanwhile, MCP-1 expression was positive in 20/48 (41.7%) of our AML cohort and was insignificantly higher in M4/M5 group (10/21, 48%) than M0/M1/M2 group (10/29, 34%) (p =0.2). Regarding EMI, lymphadenopathy was found in 90% of patients in M4/M5 group versus 30% in M0/M1/M2 group (p =0.001). Conclusion: Data suggest that MCP-1 and CXCR4 have major impact on tumor load in AML at time of diagnosis. In addition, MCP1 have a striking role in EMI irrespective of the FAB subtype. Its ligand CCR2 seems to be restricted to monocytic group (M4/M5) which showed significant lymphadenopathy when compared to M0/M1/M2 group.