Clinical Pathology: Genetic Testing

994) A bone marrow specimen from a 6-year-old boy with suspected acute leukemia was submitted for chromosome analysis. Histological examination of the bone marrow biopsy revealed complete replacement of normal cells with small to medium-sized immature blast cells (86%) with high mitotic activity. Flow cytometry analysis of the marrow in the CD45-negative gate showed immature precursor cells positive for CD19, HLA-DR, CD34, CD10, TdT, and CD22. Chromosome analysis showed loss of one copy of most of the autosomes, as shown in the figure. This karyotype is described as 27<1N>,XY,+14,+18,+21. Based on this karyotype, combined with the morphology and flow cytometry findings, which one of the following statements describes the most likely diagnosis and prognosis in this case?

• Clonal karyotypic abnormalities are seen in two-thirds of all newly diagnosed acute lymphoblastic leukemia (ALL) patients. Changes involving both chromosome number and structure are seen. These include near-haploid, hypodiploid, hyperdiploid, and pseudo-diploid karyotypes.

• The chromosome changes in B-cell ALL play an important role regarding diagnostic classification and prognosis prediction.

• Ploidy groups in ALL represent well-established cytogenetic entities comprising low hyperdiploidy (46 to 49 chromosomes), high hyperdiploidy (51 to 65 chromosomes), near triploidy (66 to 79 chromosomes, near tetraploidy (84 to 100 chromosomes), hypodiploidy (45 chromosomes), low hypodiploidy (31 to 39 chromosomes), and near-haploidy (25 to 29 chromosomes).

• Each ploidy group predicts chemotherapy responses in ALL. Overall, hyperdiploid ALL groups respond well to standard chemotherapy, compared with patients with hypodiploid and near-haploid karyotytes.

• Children with ALL with hypodiploidy karyotypes have a progressively worse outcome with decreasing chromosome numbers, even after treatment with intensive protocols.

• The near-haploid karyotype is rare, and this unique ALL patient group presents more frequently in children than in adults.

• A near-haploid karyotype is defined as having 25 to 29 chromosomes, and the majority of such cases have 26 chromosomes. This chromosome loss is not random. There is a preferential retention of disomy of chromosomes 21, X, Y, 14, and 18, in this order of frequency. Structural chromosome abnormalities are rarely seen in the near-haploid group. A near-haploid clone can also be present along with a hyperdiploid karyotype, as a result of duplication of the near-haploid karyotype. Distinguishing a hyperdiploidy clone resulting from duplication of near-haploid cells from a true hyperdiploid karyotype is extremely important, given the very different prognostic significance of these two patient groups.

• Childhood ALL patients with a near-haploid karyotype generally have a short complete remission and a dismal prognosis.

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