T-cell Chronic Leukemia Research Articles

Chronic T-cell leukemias. I. Morphology, cytochemistry and ultrastructure

The morphology and cytochemistry of 15 cases of chronic T-cell leukemia: seven of T-CLL, six of T-PLL, 2 of T-LCL and 7 cases of Sezary syndrome, have been studied by light microscopy and transmission EM. T-CLL lymphocytes had moderately abundant basophilic cytoplasm with azurophilic granules. At EM the nuclear outline was irregular, there was abundant heterochromatin and the nucleolus was inconspicuous. Varying numbers of scattered electron dense granules and PTA were seen in the cytoplasm. In T-PLL the nucleolus was large and there was little chromatin condensation. Cytoplasmic granules were grouped in one area of the cytoplasm but not PTA were seen. T-LCl cells were pleomorphic with both blasts and mature forms with very irregular nuclei. There were granules but no PTA in the cytoplasm. Sezary cells had a cerebriform or deeply cleft nucleus; cytoplasmic granules were large and scanty. AP was positive both at light microscopy and at EM level in T-CLL and was confined to the granules. AP was less strongly positive in T-PLL and some of the granules were negative; it was negative in T-LCL while it was positive in the granules of Sezary cells. ANAE showed a strong dot-like positivity in T-PLL in contrast to a weak or negative reaction in T-CLL. Our findings show that the clinically heterogeneous chronic T-cell leukemias can be distinguished from each other on morphological and cytochemical grounds. These disorders reflect the proliferation of different subsets of mature (post thymic) T-lymphocytes. T-CLL being mainly a disease of Tγ cells and Sezary syndrome (and probably T-PLL) a disease of Tμ cells.

Changes in membrane markers and chromosome patterns in chronic T-cell leukemia

A patient with asymptomatic chronic lymphocytic leukemia (CLL) and only moderate lymphocytosis has been followed for 2.5 years. Originally, surface membrane markers and response to T-cell mitogens (phytohemagglutinin, concanavalin A, A23187) indicated a T-cell neoplasm. Over time, these T-cell properties were gradually lost [e.g., cells forming sheep erythrocyte (E) rosettes decreased from 77 to 16%]. Concomitantly, an expanding chromosomally abnormal clone, including a 14q + marker, became demonstrable in peripheral blood cultures stimulated by T-cell mitogens. There has been no change in clinical course nor in the morphology of the circulating lymphocytes. The results indicate that membrane markers and chromosome patterns can change during the course of CLL, presumably reflecting the emergence of new subpopulations during clonal evolution of the disease. In this instance, clinical progression has not occurred simultaneously, and additional data are needed to determine the prognostic value of such longitudinal studies.

Neutrons against Cancer

Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22–23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22–23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22–23. Loss of heterozygosity at 11q22–23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL. To determine whether the ATM gene is altered in B-CLL, we have sequenced individual ATM exons in six B-CLL cases. We show that the ATM gene is mutated in a fraction of B-CLLs and that mutations can be present in the germ line of patients, suggesting that ATM heterozygotes may be predisposed to B-CLL.