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Annals of Clinical & Laboratory Science, vol. 40, no. 3, 2010
273
Constitutional Pericentric Inversion 9 and Hematological Disorders: A Korean Tertiary Institution’s Experience over Eight Years
Sang-Guk Lee,1 Tae Sung Park,2 Gayoung Lim,2 Kyung-A Lee,1 Jaewoo Song,1 and Jong Rak Choi1 of Laboratory Medicine, Yonsei University College of Medicine, Seoul; 2Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
1Department
Abstract. Constitutional pericentric inversion of chromosome 9 [inv(9)] occurs in 0.8 to 2% of the normal population and has long been considered a normal variant. It is controversial whether inv(9) is a predisposing factor for acute leukemia (AL). The effect of inv(9) on bone marrow (BM) recovery after stem cell transplantation or chemotherapy is undetermined. Between March 2001 and December 2008, the cytogenetics of 3,809 patients with suspected hematological diseases were reviewed. Of them, 586 patients were diagnosed with AL. Constitutional inv(9) was found in 55 patients with various hematological disorders, including AL and solid tumors. The proportion of inv(9) was similar in patients with AL (8/586, 1.37%) and those without (47/3223, 1.46%; p = 1.0). Of the eight patients with AL and inv(9), one refused treatment and seven had induction chemotherapy. Four of the seven patients achieved prompt hematological recovery, but the other three failed to achieve complete hematological remission. Thus constitutional inv(9) seems not to be related independently to delayed hematological recovery. One recipient of an allogeneic peripheral blood stem cell transplantation, from an unrelated donor with constitutional inv(9), also achieved prompt hematological reconstruction, further suggesting that constitutional inv(9) has no effect on hematopoietic cells. In summary, our data suggest that constitutional inv(9) is a truly random chromosomal aberration with no apparent functional effect on hematological disorders. Keywords: chromosome inversion, chromosome 9, acute leukemia, bone marrow recovery Introduction Constitutional pericentric inversion of chromosome 9 [inv(9)] occurs in 0.8 to 2% of the normal population [1,2]. The breakpoints of inv(9) are located preferentially at 9p12 and 9q13-21.1, and less frequently at 9q12 [3,4]. Study of the heterochromatin organization in the pericentromeric region has revealed homology between 9p11Address correspondence to Tae Sung Park, M.D., Ph.D., Department of Laboratory Medicine, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea; tel 822 958 8673; fax 822 958 8609; e-mails
[email protected] or
[email protected]; or Jong Rak Choi, M.D., Ph.D., Department of Laboratory Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea; tel 822 2228 2445; fax 822 313 0956; e-mail
[email protected].
12 and 9q13-21.1. Such homologous sequences could be involved in the mechanism that generates the inversion [3]. Although it is generally regarded as a normal variant, inv(9) has been implicated in infertility, recurrent abortion [5–7], schizophrenia [8,9], bipolar disorder [10], and myotonic dystrophy [11]. Whether constitutional inv(9) is a predisposing factor for cancer is controversial. However, there is evidence to suggest that it might predispose to the development of laryngeal carcinoma [12] and ovarian cancer [13]. Several studies have compared the frequency of inherited inv(9) in patients with acute leukemia (AL) vs healthy controls. However, the results were inconsistent [14–17]. The effect of inv(9) on bone marrow (BM) recovery after stem cell transplantation or chemotherapy has been evaluated [14,18–21], but these results were also inconclusive. We have studied retrospectively the
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274 Annals of Clinical & Laboratory Science, vol. 40, no. 3, 2010 incidence and clinical significance of inv(9) in a large series of patients whose BM karyotypes were collected during an eight-year period at the Yonsei University Healthcare System. Materials and Methods Patient material. Between March 2001 and December 2008, BM examination and cytogenetics were performed at Yonsei University Healthcare System in 3,809 patients with suspected hematological diseases. The cytogenetics were reviewed with available clinical data. Repeated cytogenetic results from the same patients were not included. Cytogenetics. A standard culture technique for BM cells was applied and chromosomes were analyzed using the Giemsa banding technique. The karyotype was described according to the International System for Cytogenetic Nomenclature (ISCN 2009) [22]. Clinical significance of inv(9). In the cases of AL with constitutional inv(9), clinical and laboratory data were obtained from the patients’ medical records. We noted the clinical outcome, time from induction chemotherapy to recovery of absolute neutrophil count (ANC) >0.5×109/L, and platelet count >20×109/L without platelet transfusion. When ANC and platelet count were not decreased
