VOLUME 15 (Supplement)

A study on complex karyotypes in leukemia by routine G-banding and whole chromosome painting: A report on four Filipino cases

Cytogenetic or chromosome abnormalities seen in leukemia patients at diagnosis are used to stratify patients into various risk groups and also serve as predictors of disease progression and response to therapy. Routine cytogenetic analysis using G-banding remains the standard procedure in establishing normal as well as abnormal karyotypes. But this method has its own resolution issue so describing multiple chromosome aberrations in complex karyotypes is challenging. This paper aims to document complex karyotypes (CK) in Filipino leukemia patients seen at diagnosis and at the same time compare the strengths and limitations of routine karyotyping and whole chromosome painting (WCP) technology (either SKY or M-FISH platforms). Follow-up cytogenetic analyses and clinical correlation of results were not done on these cases. There are four adult leukemia cases presented: two acute, one chronic, and one unclassified that were found with complex karyotypes using routine cytogenetic banding technique (GTG banding) and subsequently verified either by SKY or M-FISH. Case # 1 was a 39-year old male diagnosed with AML whose initial karyotype was 46,XY,t(3;20)(q13;q13.2). This finding was confirmed in SKY with an additional t(9;22)(q34;q11.2) aberration. Case #2 was a 37-year old male with a complex karyotype, 48,XY,ins(1)(q21q24q31), inv(1)(p2?1p3?6.1),+8,+8. SKY confirmed the presence of two extra copies of chromosome 8, but not the insertion and inversion in chromosome 1 pair. Case # 3 was a 87-year old female initially diagnosed with anemia but was found to carry a complex karyotype 45,XX,t(2;4) (q11.2;q35),del(5)(p11), add(17)(p13),+mar. SKY confirmed the abnormalities in chromosomes 2,4,5 and 17 and trisomy 8. The composition of the marker chromosome was revealed coming from chromosomes 2,4 and 14; and the additional material on 17p was a segment of chromosome 5. Nine minute chromosomes or acentric fragments not earlier reported by G-banding were also observed. Lastly, case #4 was a 41-year old male with chronic myelogenous leukemia (CML) presenting an atypical karyotype 47,XY,+8,t(12;17)(p13;q23). M-FISH confirmed all these abnormalities. Complex karyotypes presented in this paper demonstrated the advantages and limitations of both technologies. Identification of aberrant chromosomes by G-banding provided a good take off point in identifying directly the aberrant genomic segments and indirectly the genes lying in these segments that may have been disrupted and altered and are believed to contribute to the malignancy. Whole chromosome paint technology using either SKY or M-FISH was very useful in describing marker chromosomes and acentric fragments, as well as in verifying segments involved in translocation. However, it failed to recognize structural rearrangements within the same chromosome pair. The tandem of routine G-banding technique and SKY paint proved to be an accurate and powerful approach in identifying chromosome abnormalities especially in complex karyotypes.