Beta-2 Microglobulin in AML
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In a large series of acute myelogenous leukemia patients, elevated serum beta-2 microglobulin was found to be an independent negative prognostic factor with regard to overall survival, but was significant only for those over the age of 60 years. This finding may be of value in identifying those elderly patients least likely to benefit from conventional treatment approaches.
Source: Tsimberidou AM, et al. Clin Cancer Res. 2008;14:721-730.
Beta-2 microglobulin (b2M) is a structural subunit of the HLA complex.1 Upon degradation of HLA as often occurs during cellular proliferation, b2M is dissociated from the complex, released into the extracellular fluid and ultimately filtered and reabsorbed by the kidney. Thus, b2M serum levels are known to reflect both membrane turnover and renal function. Elevated levels of b2M have been reported in lymphoid malignancies, multiple myeloma, chronic myelogenous leukemia, and myelodysplastic syndrome, as well as in certain other malignant conditions.2-5
The purpose of the current study was to determine whether serum levels of b2M provide prognostic information in patients with acute myelogenous leukemia. This was addressed by Tsimberidou and her colleagues at M.D. Anderson in an evaluation of 1180 patients treated at that institution between 1985 and 2005.
Multivariate analyses were undertaken to examine the effect of pretreatment serum b2M level on clinical outcomes including survival, event-free survival, and relapse-free survival. The methodology included examining data from one half of the entire group of patients, developing a prognostic panel including serum b2M and then validating the model using data from the second half of patients.
In those 60 years or older (n = 591), cytogenetic abnormalities, poorer performance status, and higher levels of b2M, uric acid, and lactate dehydrogenase (LDH) were found to independently predict shorter survival. For younger patients (< 60 years; n=589), cytogenetic abnormalities, poor performance status, older age (within this age group), lower hemoglobin level, and higher leukocyte count were all negative predictors. These factors were used to construct a model for predicting prognosis. It was notable that higher b2M level was an independent factor in older but not younger patients when examined independently.
Commentary
As has been demonstrated with other bone marrow and lymphoid malignancies, serum b2M level was found to be an independent risk factor in acute myelogenous leukemia, but interestingly, only for those patients 60 years and older. An explanation for this age discrepancy is unclear, but it does serve as yet another reminder that acute leukemia in the elderly is quite different than in the young.6
Why b2M would be an adverse prognostic indicator at all also remains unsolved. b2M, a component of the HLA molecular complex, is known to be variably expressed on the surface of a number of tumor cells and, at least for lymphomas, a poor expression is considered an adverse prognostic factor. This may relate to the host response to tumor antigen, which depends on an intact HLA expression. Thus, malignant cells with modified or lacking HLA expression may escape from normal host immune response and proliferate uncontrollably.7,8
Thus, the data from this large, consecutive series of AML patients indicate that serum b2M levels are highly predictive for clinical outcomes in patients over the age of 60 with newly diagnosed AML. The scoring system introduced, which includes all the prognostic factors that proved to be independently significant (cytogenetics, performance status, and b2M, uric acid, and LDH levels) may be an advance in defining those patients with favorable or unfavorable prognosis and adjusting therapeutic approaches accordingly.
References
1. Bjorkman PJ, et al. Nature. 1987;Oct 8-14;329(6139):506-512.
2. Chronowski GM, et al. Cancer. 2002;(12):2534-2538.
3. Durie BG, et al. Blood. 1990;(4):823-830.
4. Litam P, et al. Ann Intern Med. 1991;114(10):855-860.
5. Rodriguez J, et al. Clin Cancer Res. 2000 Jan;6(1):147-152.
6. Ballester O, et al. J Am Geriatr Soc. 1992;40(3):277-284.
7. Tanaka K, et al. Science. (New York, NY 1985 Apr 5;228(4695):26-30.)
8. Zinkernagel RM, Doherty PC. Adv Immunol. 1979;27:51-177.
In a large series of acute myelogenous leukemia patients, elevated serum beta-2 microglobulin was found to be an independent negative prognostic factor with regard to overall survival, but was significant only for those over the age of 60 years.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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