Johan Billiet

Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low‐risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I–II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases.  In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL.  Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.

Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans

Background.  Autologous transplantation of bone marrow mononuclear cells (ATBMMNC) has been used successfully in critical limb ischemia. All reported patients were of Asian descent, however, and several studies included only young patients with thromboangiitis obliterans. Whether the beneficial results can be extrapolated to older Caucasian patients with atherosclerosis obliterans and a heavy burden of cardiovascular risk factors remains unclear.

Ruxolitinib inhibits transforming JAK2 fusion proteins in vitro and induces complete cytogenetic remission in t(8;9)(p22;p24)/PCM1-JAK2–positive chronic eosinophilic leukemia

To the editor: The JAK1/JAK2 inhibitor ruxolitinib was recently approved for intermediate and high-risk myelofibrosis. However, for malignancies with JAK2 rearrangements, known for their rapid evolution and dismal prognosis, the potential of JAK inhibitor therapy is not established.[1][1] We

X-linked sideroblastic anemia and ataxia: a new family with identification of a fourth ABCB7 gene mutation

X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare cause of early onset ataxia, which may be overlooked due to the usually mild asymptomatic anemia. The genetic defect has been identified as a mutation in the ABCB7 gene at Xq12-q13. The gene encodes a mitochondrial ATP-binding cassette (ABC) transporter protein involved in iron homeostasis. Until now only three families have been reported, each with a distinct missense mutation in this gene. We describe a fourth family with XLSA-A and a novel mutation in the ABCB7 gene.

Analysis of phenotype and outcome in essential thrombocythemia with CALR or JAK2 mutations

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival.

The JAK2V617F mutation can occur in a hematopoietic stem cell that exhibits no proliferative advantage: a case of human allogeneic transplantation

To the editor: In 1998 a female patient received an allogeneic stem cell (SC) transplant from her sister 9 months after she was diagnosed with a high risk myelodysplastic syndrome (RAEB2) and was treated with chemotherapy aiming to achieve complete remission. A myeloablative conditioning regime was

Leukaemic Intermediate Lymphocytic Lymphomas: Analysis of Twelve Cases Diagnosed by Morphology

Twelve cases of leukaemic intermediate diffuse lymphocytic lymphoma (ILL), diagnosed by morphology, were analysed. The morphology of the ILL cells was so typical that it allowed ready distinction from chronic lymphocytic leukaemia (CLL) and other related B cell disorders. All cases were of B derivation, had strong mu and chi or lambda immunoglobulin (Ig) staining, were CD5 and FMC7 positive and CD10 negative. Cytogenetic abnormalities were found in 8 patients all having t(11;14)(q13;q32). DNA analysis revealed a relatively high incidence of hypoploidy. At diagnosis all the patients (9 males, 5 females; median age 68) had a low degree of absolute lymphocytosis but the disease was advanced and mostly widespread. The course of the disease appears to be aggressive and incurable with conventional combination chemotherapy.