Dynamic Changes in the Levels of sCD62L and SPARC in Chronic Myeloid Leukemia Patients During Imatinib Treatment

Tanta University

Status: Completed

Conditions: Chronic Myeloid Leukemia

Treatments: Diagnostic Test: ELISA kit

Study type: Observational

Funder types: Other

Identifiers

NCT05387330

9093595

Details and patient eligibility

About

This study aims to monitor the levels of soluble L-selectin (sCD62L) and secreted protein acidic rich in cysteine (SPARC) in chronic phase chronic myeloid leukemia (CP-CML) patients at baseline and after three and six months of imatinib therapy and evaluated the effect of imatinib on their levels and correlated their levels to clinical and laboratory parameters.

Full description

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the reciprocal t (9:22) chromosomal translocation. This rearrangement produces abnormal chromosome called Philadelphia chromosome carrying the chimeric BCR-ABL oncoprotein which encodes for tyrosine kinase (TK). The Break Point Cluster Region- Abelson (BCR-ABL) fusion oncoprotein activates the various downstream signaling pathways causing reduced hematopoietic cell differentiation, decreased apoptosis, enhance proliferation and survival of leukemic cells. CML remains incurable for the most part, and only allogeneic hematopoietic stem cell transplantation can eradicate and cure CML. This is probably because quiescent leukemic stem cells are resistant to tyrosine kinase inhibitors (TKIs).

Imatinib (IM) was the first tyrosine kinase inhibitor to receive approval by the Food and Drug Administration for the treatment of patients with CML-CP. It acts via competitive inhibition at the ATP - binding site of the BCR-ABL protein, which results in the inhibition of phosphorylation of proteins involved in signal transduction. It inhibits the BCR-ABL kinase.

L-selectin is a glycoprotein which is one of three members in a family of cell adhesion molecules called selectins. L-selectin is expressed on most leukocytes and it appears to play an important role in the early stages of leukocyte-endothelial cell interaction. L-selectin is a critical molecule for the leukocyte-endothelial cell interaction that results in migration of naïve T-cells into peripheral lymph nodes and inflammatory locales such as: tumor microenvironment.

Secreted Protein, Acidic Rich in Cysteine (SPARC) is a multi-functional matricellular glycoprotein with growth inhibitory and anti-angiogenic activity in some cell types. This protein has counter adhesive properties, has effects on cell shape, immune surveillance, angiogenesis and inhibits cell proliferation. SPARC is multifunctional calcium binding matricellular glycoprotein, participates in tissue remodeling, morphogenesis and bone mineralization and is secreted by different types of cells such as: osteoblasts, fibroblasts and endothelial cells. SPARC binds Vascular Endothelial Growth Factor (VEGF), preventing VEGF induced tyrosine phosphorylation of VEGFR1 and antagonizing its pro-angiogenic effects. The role of SPARC in tumor genesis appears to be cell-type specific due to its diverse function in given microenvironment.

sCD62L and SPARC analyzed using commercially available ELISA kit.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Both sexes.
• Newly diagnosed patient with chronic phase, Philadelphia chromosome positive (Ph+) CML.
• Age ≥ 18 years.

Exclusion criteria

• Patients in blastic or accelerated phase of chronic myeloid leukemia.
• Previous treatment with Imatinib.
• Pregnancy and lactation.
• Severe hepatic dysfunction.
• Kidney dysfunction.
• Intolerant or incompliant to imatinib.

Trial design

35 participants in 2 patient groups

CP-CML patients

Description:

Twenty five newly diagnosed CP-CML patients. Plasma sCD62L and serum SPARC levels were measured using commercially available ELISA kits

Treatment:

Diagnostic Test: ELISA kit

Control

Description:

Ten matched controls were enrolled. Plasma sCD62L and serum SPARC levels were measured using commercially available ELISA kits

Treatment:

Diagnostic Test: ELISA kit