SYNDROME OF ABNORMAL CHROMATIN CLUMPING IN LEUKOCYTES WITH A HIGH FRACTION OF BONE-MARROW CELLS IN S-PHASE AND IN-VITRO AUTONOMOUS GROWTH

Syndrome of abnormal chromatin clumping in leucocytes syndrome (ACCLS) is an uncommon entity which shares clinical and biological features w ith the myelodysplastic (MDS) and chronic myeloproliferative syndrome. In fact, as some authors consider ACCLS a new type of MDS, others mai ntain that it is in Ph'negative/bcr-abl negative chronic myeloid leuka emia. A new case of ACCLS appeared in a 68 year old woman, who present ed with anaemic symptoms, bleeding and recurrent infections, and a hae matological picture including progressive macrocytic anemia, thrombocy topenia and leuco-erythroblastosis. Marrow hypercellularity with granu locytic hyperplasia, and mature granulocytes presenting nuclear hypose gmentation and large peripheral blocks of chromatin separated by clear zones were the characteristic features of this case. No cytogenetic a bnormalities were found and DNA flow-cytometry content was normal (eup loid), supporting the thought that a disequilibrium exists in the hete ro-chromatin/eucromatin ration in AACLS. Reverse PCR for bcr-abl trans critps was negative. The cell-cycle-phase analysis showed a high fract ion of S-cells in the bone marrow (27%) in contrast to a very low S-ph ase (0.2%) in the peripheral blood, pattern that is different from bot h CMML and CML. In vitro clonogenic assays showed a high colony formin g capacity and a certain grade of autonomous proliferation of the bone marrow cells, which is reminiscent of the CMML growth behaviour in cu lture. The patient was treated with vitamin D-3, low dose Ara-C, predn isone and hydroxyurea until her demise, fifteen months after diagnosis . In total, the patient received 47 units of packed cells and 114 of p latelet concentrates, and was transfused only when she presented anaem ic or hemorrhagic symptoms. These clinical and haematological features suggest that ACCLS is a distinct entity that should be considered a s ixth type of MDS, beside CMML, with which it has much in common.