摘要：
Abstract 4427
Very rarely, Philadelphia positive (Ph+) chronic myeloid leukemia (CML) presents with isolated thrombocythemia (CML-T) with no or only slight elevation of neutrophil counts. Due to their rarity, such patients have not been studied in detail, especially whether they constitute a separate disease entity, where the initiating leukemic hit originates from a more lineage-committed progenitor cell type than the one affected in classical CML. To evaluate this, we studied a 68-year-old woman who during a follow-up for follicular lymphoma presented with a sudden thrombocythemia of 2062×109/L, a basophil count of 0.94×109/L but no increase in neutrophil count (3.9×109/L). A bone marrow (BM) biopsy revealed slight to moderate hyperplasia with an increased number of small, hypolobulated megakaryocytes, but no increase in the myelopoietic compartment. Apart from the Ph1 positivity, no molecular aberrations were seen by cytogenetic analysis, array CGH, or extensive molecular testing; noteworthy, the JAK2 V617F mutation was absent. The patient was treated with three different Tyrosine Kinase Inhibitors (TKI’s), all of which had to be terminated after a total of 26 weeks of therapy due to severe side effects (dyspnea, acrocyanosis of the fingers and fatigue). At present, she is on pegylated interferon alpha-2a, which is well tolerated.
In a longitudinal study of the stem cell biology in this patient we centered on three BM aspirates obtained at diagnosis as well as 3 and 9 months following diagnosis. Subsets of progenitor- and mature lineage committed cells were FACS-purified and analyzed for the presence of leukemic cells by FISH and qPCR technique and additionally subjected to growth in a 14-day methylcellulose assay. At diagnosis, the CD34+ compartment consisted of 10% immature (CD34+CD38-) and 90% mature (CD34+CD38+) progenitors, both of which were enriched for Ph+ cells (74% and 78%, respectively) (Figure 1A-B). Moreover, the colony-forming cells (CFC's) from
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