Levels of soluble HLA-I and β2M in patients with acute myeloid leukemia and advanced myelodysplastic syndrome: association with clinical behavior and outcome of induction therapy

Albitar, Mäher; Johnson, M. M.; A., K.; Day, Amanda; Jilani, Iman; Pierce, Sherry; Estey, Elihu H.; Kantarjian, Hagop M.; Keating, Michael J.; Verstovšek, Srđan; O’Brien, Susan; Giles, Francis J.

doi:10.1038/sj.leu.2404506

Cited by 22 publications

(19 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other negative clinical prognostic variables include depth of cytopenias, higher lactate dehydrogenase and beta-2 microglobulin levels, marrow fibrosis, poor co-morbidity index, certain flow cytometry-associated aberrant CD34 co-expression patterns (Table I) (Albitar et al, 2007;Haase et al, 2007;Kao et al, 2008;Zipperer et al, 2009). In addition, recent molecular studies have indicated that both single gene mutations (e.g.…”

Section: Mds Classificationsmentioning

confidence: 99%

Current therapeutic approaches for patients with myelodysplastic syndromes

Greenberg

2010

Br J Haematol

View full text Add to dashboard Cite

SummaryThe myelodysplastic syndromes (MDS) are a heterogeneous spectrum of disorders requiring selective therapy based on patients' specific clinical features, predominantly their prognostic subgroups, age and performance status. Guidelines for management of patients with MDS have been generated by a number of national panels. This review focuses on evidencebased data supporting therapeutic approaches, which have also been recommended by the US National Comprehensive Cancer Network MDS Panel, with discussion of accessibility of recommended drugs in the US and in other countries. For lower risk disease (International Prognostic Scoring System Low and Intermediate-1) therapy is aimed at haematological improvement whereas for higher risk disease (Intermediate-2 and High) treatment focuses on altering disease natural history. Recent information regarding additional clinical and biological features has provided useful parameters for assessing disease prognosis that aid risk-based management decisions. The rationale for use of low versus high intensity therapies with these agents, including allogeneic haematopoietic stem cell transplantation, is discussed in detail.

show abstract

Section: Mds Classificationsmentioning

confidence: 99%

Current therapeutic approaches for patients with myelodysplastic syndromes

Greenberg

2010

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…It has been known for a while that the levels of the soluble HLA class I molecules (sHLA-I) are elevated in the serum of people inflicted with diseases, such as cancer (9)(10)(11)(12)(13), autoimmunity (14), allergy (15), and viral infections (16). Such elevated levels of sHLA were even proposed to serve as indicators of poor prognosis (11,17), yet their bound peptidomes have never been analyzed before.…”

mentioning

confidence: 99%

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

Bassani-Sternberg

Barnea

Beer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

120

133

View full text Add to dashboard Cite

The HLA molecules are membrane-bound transporters that carry peptides from the cytoplasm to the cell surface for surveillance by circulating T lymphocytes. Although low levels of soluble HLA molecules (sHLA) are normally released into the blood, many types of tumor cells release larger amounts of these sHLA molecules, presumably to counter immune surveillance by T cells. Here we demonstrate that these sHLA molecules are still bound with their authentic peptide repertoires, similar to those of the membranal HLA molecules (mHLA). Therefore, a single immunoaffinity purification of the plasma sHLA molecules, starting with a few milliliters of patients' blood, allows for identification of very large sHLA peptidomes by mass spectrometry, forming a foundation for development of a simple and universal blood-based cancer diagnosis. The new methodology was validated using plasma and tumor cells of multiple-myeloma and leukemia patients, plasma of healthy controls, and with cultured cancer cells. The analyses identified thousands of sHLA peptides, including some cancer-related peptides, present among the sHLA peptidomes of the cancer patients. Furthermore, because the HLA peptides are the degradation products of the cellular proteins, this sHLA peptidomics approach opens the way for investigation of the patterns of protein synthesis and degradation within the tumor cells.

show abstract

“…Elevated serum h2M levels are reported to predict poor survival in several hematologic malignancies, which include multiple myeloma (11), low-grade lymphomas (12), large-cell lymphomas (13 -15), Hodgkin's lymphoma (16,17), acute lymphoblastic leukemia (18), Philadelphia chromosome -positive chronic myeloid leukemia (19), chronic lymphocytic leukemia (20,21), and myelodysplastic syndromes (22,23).…”

mentioning

confidence: 99%

“…However, prognostic heterogeneity still exists and novel prognostic factors are being developed. Although some reports on the prognostic significance of h2M in AML have been published (23,36,37), the independent prognostic role of h2M in AML has not been established. Here, we examine whether h2M level is an independent prognostic factor in untreated AML that could be added to known prognostic factors to reduce prognostic variation.…”

mentioning

confidence: 99%

The Prognostic Significance of Serum β2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Patients

Tsimberidou¹,

Kantarjian²,

Wen

et al. 2008

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Serum h 2 microglobulin (h2M) is prognostic in other hematologic malignancies; therefore, we evaluated its prognostic significance in acute myeloid leukemia (AML). Experimental Design: Multivariate analyses were used to examine the effect of pretreatment serum h2M levels on clinical outcomes in patients with AML. h2M was associated with poorer survival in older but not younger patients. We thus fit separate Cox survival models in patients above and below age 60 years treated with remission induction therapy containing high-dose cytarabine (n = 1,280). In each age group, 50% of the patients were used to develop the model, which was tested in the other 50%. Resampling methods were also used to validate the independent prognostic significance of covariates. Results: In patients 60 years or older (n = 591), poorer risk cytogenetics; poorer performance status; and higher levels of h2M, uric acid, and lactate dehydrogenase were each found to independently predict shorter survival and formed the basis of a scoring system. A similar approach was used in patients younger than 60 years (n = 589), with poorer risk cytogenetics, poorer performance status, older age, higher hemoglobin level, and higher leukocyte count predicting a shorter survival and forming the basis of the scoring system. Higher h2M levels were an adverse independent factor for response, survival, relapse-free survival, and event-free survival in older but not in younger patients. Conclusions: Serum h2M levels can help predict outcome in patients z60 years with untreated AML, and their use is strongly encouraged.

show abstract

Levels of soluble HLA-I and β2M in patients with acute myeloid leukemia and advanced myelodysplastic syndrome: association with clinical behavior and outcome of induction therapy

Cited by 22 publications

References 40 publications

Current therapeutic approaches for patients with myelodysplastic syndromes

Current therapeutic approaches for patients with myelodysplastic syndromes

Soluble plasma HLA peptidome as a potential source for cancer biomarkers

The Prognostic Significance of Serum β2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Patients

Contact Info

Product

Resources

About