Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster I
Interphase chromosome Profiling (ICP) is a new novel molecular cytogenetic technology which is capable of producing a complete molecular karyotype from interphase nuclei of any tissue without the need for tissue culture. ICP has been demonstrated to be a failure proof technology with greater sensitivity to detection of large and/or cryptic cytogenetic aberrations than standard cytogenetics and FISH, and can also characterize marker chromosomes and chromosomal material of unknown origin in unbalanced rearrangements. (Cytogenet Genome Res 2014;142:226, Abstract #22). Besides the common deletions and monosomies involving the chromosomes 5, 7 and 20; and trisomy 8, several balanced translocations have been identified in MDS which cannot be detected by the current MDS-FISH panel. Additionally, other abnormalities present in both simple and complex karyotypes will be missed by MDS-FISH. ICP has been developed to detect most of these changes in both BM and PB samples.
We have tested the utility of ICP on eight peripheral blood and two bone marrow samples from 10 MDS cases. Two of these had no karyotype results. Four had a normal karyotype and the other four had a normal MDS-FISH. Both BM samples had a normal karyotype. One had a history of AML with trisomy 8, but was not detected in the current relapsed sample. Two cases had additional clinical suspicion of CLL or Multiple Myeloma in addition to MDS.
ICP was successful in all ten samples and the normal molecular karyotype is concordant with either the cytogenetics or FISH result. In the two failed cytogenetic cases and no FISH study, ICP showed a normal result. The guidelines for establishing the clonality when utilizing the ICP technology is in progress (manuscript in preparation). In the ICP validation studies referenced above, any abnormality present in four or more cells in a 20 cell analysis is considered positive and was always corroborated by either cytogenetics or FISH studies. However, in couple of patients, the clonal abnormality identified by FISH studies, was present in only two to three cells in the ICP study. At present, the clinical significance of these “minor” clones identified by ICP analyses is not clear. Large prospective studies are needed to answer this question. We have identified such minor clonal abnormalities in two of the ten cases in three to four cells. These abnormalities include marker chromosomes and potential balanced translocations involving chromosomes 1, 2, 12, and 14. As mentioned above, current MDS-FISH will not detect these minor clones but identified by the ICP technology and may be clinically significant.
Our results clearly demonstrate that ICP is a very sensitive technology and may be considered and adopted as the preferred method of choice in the initial screening of MDS patients especially on peripheral blood samples.
Disclosures: No relevant conflicts of interest to declare.
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