title: Centrosome Aberration Frequency and Disease Association in B-Acute Lymphoblastic Leukemia.
abstract: Recent developments in genome-wide genetic analysis in B-acute lymphoblastic leukemia (B-ALL) have provided insight into disease pathogenesis and prognosis. B-ALL cases usually carry a primary genetic event, often a chromosome translocation, and a constellation of secondary genetic alterations that are acquired and selected dynamically in a nonlinear fashion. As far as we are aware of, for the first time, we studied centrosome aberration in patients with B-ALL to understand the progression of the disease. A cytogenetic study was carried out by GTG-banded karyotyping and fluorescence in situ hybridization. DNA index study was carried out with flow cytometry. Indirect immunostaining of centrosomes was performed on mononuclear cells using primary and corresponding secondary antibodies for centrosome-specific protein γ-tubulin. Three primary and corresponding secondary antibodies to three different centrosome-specific proteins, namely α-tubulin, γ-tubulin and pericentrin, were used for indirect immunostaining. The study was carried out on 50 patients with B-ALL. Centrosomal abnormalities were detected in 36 (72%) patients and the remainder (28%) had normal centrosome structure and numbers. Out of these 36 patients with abnormal centrosome, structural abnormalities were detected in 12 (33.3%) and numerical abnormalities in six (16.6%). Both structural and numerical aberrations were detected in 18 (50%) patients. When correlated with the cytogenetic and DNA index findings, 26/27 (96.2%) patients had centrosome defects concomitant with both abnormal karyotype and aneuploidy. Out of 50 patients with B-ALL, 17 (34%) had normal karyotype detected by both karyotype and DNA index, among these, seven (41.17%) patients had centrosome aberration. The morphological and structural abnormalities of the centrosome present in B-ALL cells have a role in disease development and can be considered as prognostic markers.
authors.affiliation: National Institute of Immunohematology, Parel, Mumbai, India.
authors.forename: Lily S
authors.initials: LS
authors.lastname: Kerketta
authors.affiliation: National Institute of Immunohematology, Parel, Mumbai, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: National Institute of Immunohematology, Parel, Mumbai, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Nadkarni
authors.affiliation: National Institute of Immunohematology, Parel, Mumbai, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
authors.affiliation: National Institute of Immunohematology, Parel, Mumbai, India vbaburao@hotmail.com.
authors.forename: Babu Rao
authors.initials: BR
authors.lastname: Vundinti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000941:Antigens / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D014404:Tubulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D000941:Antigens; D014404:Tubulin; C086178:pericentrin
keywords: B-ALL; centrosome aberrations; chromosomal abnormalities; hyperdiploidy; polyploidy; prognosis