The syndrome of abnormal chromatin clumping in leucocytes: a myelodysplastic disorder with proliferative features?

Abstract

Five patients presenting extremely exaggerated chromatin clumping in leucocytes, associated with a loss of segmentation, are described. Peripheral cytopenia, a high percentage of circulating immature granulocytes (chiefly myelocytes) with variable leucocytosis, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines, constitute, together with the granulocytic nuclear anomaly, the characteristic features of the studied cases. Cytogenetic analysis showed a clonal 12p anomaly in one of the three cases available for study. Survival was poor with a median of 15 months, bleeding and infections being responsible for the majority of deaths. All these findings point to abnormal chromatin clumping in leucocytes as the marker of a true entity with both myelodysplastic and myeloproliferative features. We propose that it take its place among myelodysplastic syndromes (MDS) beside chronic myelomonocytic leukaemia (CMML), with which it shares many similarities in clinical and biological behaviour.

Cytogenetics and Its Prognostic Value in Myelodysplastic Syndromes

“…Similar observations have also been made in chronic myeloid leukemia with involvement of 17p in the blast phase [31]. Another pathologic feature of the granulocytic series is clumping of the nuclear chromatin, which has been associated with a deletion of the short arm of chro mosome 12 [32].…”

The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features

“…The 'syndrome of abnormal chromatin clumping' [17][18][19][20] can be considered as a variant of aCML. 10 In most patients, the WBC count is increased, but occasional patients may have normal values.…”

“…Survival times are similar to those reported in aCML. 10,[17][18][19][20] Chronic myelomonocytic leukemia CMML is a MDS/MPN whose typical manifestation is its peripheral blood monocytosis. 12,[21][22][23][24][25] The incidence of CMML is approximately three cases per 100 000 individuals older than 60 years.…”

Rarity of dominant-negative mutations of the G-CSF receptor in patients with blast crisis of chronic myeloid leukemia or de novo acute leukemia

“…About 20% of blasts were positive for CD15 and CD33. A diagnosis of secondary acute myeloid leukemia (FAB type M1) evolving from myelodysplasia, with abnormal chromatin clumping syndrome 16 was made. Cytogenetic studies of bone marrow and peripheral blood specimens showed a complex aberrant karyotype: 42−43,XX,del(1)(q42), −5, del(7)(q21), add(9)(p22), −12, −16, −17, add(17)(q25), del(18)(q21), −20, +1−2 mar.…”