Common association of haemolytic uraemic syndrome with invasive Streptococcus pneumoniae infection in five Chinese paediatric patients.

Haemolytic uraemic syndrome is an important cause of acute renal impairment in childhood. We review the incidence, and clinical and laboratory features of haemolytic uraemic syndrome in a Chinese population. Five patients were identified from 2006 to 2008. All patients were young children with associated invasive Streptococcus pneumoniae pulmonary infection. Serotypes 3, 14, and 19A were confirmed in four patients. The classical post-diarrhoeal form associated with Escherichia coli (O157:H7) infection was not seen. One patient died of acute respiratory failure. Streptococcus pneumoniae infection, as an associated condition in haemolytic uraemic syndrome, is important and relatively common in Chinese patients, especially among children. The acute clinical picture is similar to that reported in the western literature, except for an uncommon association with meningitis. The medium-term renal outcome of the Chinese population appears to be more favourable than the Caucasians. Widespread vaccination against Streptococcus pneumoniae may have resulted in changes in bacterial epidemiology and clinicians should be continuously aware of this severe disease. The use of washed blood components for transfusion in the acute stage requires further study.

The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of beta-thalassaemia.

BACKGROUND: Fetal haemoglobin (HbF) level modifies the clinical severity of HBB disorders. Intergenic variants of HBS1L-MYB on chromosome 6q23 have recently been shown to be a major quantitative trait locus (QTL) influencing HbF levels in normal Caucasian adults. METHODS: A unique and well-characterised cohort of 238 Chinese subjects with beta-thalassaemia trait was used to conduct a single-nucleotide polymorphism (SNP) association study for HbF level. RESULTS: Within this locus, 29 trait-associated SNPs in a non-coding 56 kb segment were identified. They were divided into five linkage disequilibrium (LD) blocks in the Chinese participants. CONCLUSIONS: The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of beta-thalassaemia. Functional studies to unravel the biological significance of this region in regulating HbF production is clearly indicated, which may lead to new strategies to modify the disease course of severe HBB disorders.

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome.

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

Large cell transformation of Sézary syndrome. A conventional and molecular cytogenetic study.

Hyperdiploidy sometimes is found in mycosis fungoides-Sézary syndrome, but its diagnostic significance remains undefined. We report an unusual case of Sézary syndrome manifesting with leukemic large cell transformation. Conventional karyotypic analysis showed the presence of a near-tetraploid neoplastic clone. With dual-color cytometric analysis, we showed that the large Sézary cells were near-tetraploid with a DNA index of 1.86, thereby demonstrating a direct relationship between cell size and ploidy. Comparative genomic hybridization further showed chromosomal imbalances that were not revealed on conventional karyotyping. Our findings suggest that hyperdiploidy may be a marker of large cell transformation, so that when this karyotypic abnormality is found in mycosis fungoides-Sézary syndrome, a search for such a complication is indicated.

Waldenström macroglobulinemia with karyotypic aberrations involving both homologous 6q.

An 84-year-old female presenting with proptosis and hyperviscosity syndrome was found to have Waldenström macroglobulinemia. Karyotypic analysis showed structural chromosomal abnormalities involving both homologous chromosomes 6 with a deleted 6q at q21-q23 and a complex three-break rearrangement in the t(6;13;21)?(q21;q14;q11). A literature review suggests that deletions of chromosome 6 at 6q21 are associated with lymphoplasmacytoid differentiation and IgM production in B-cell chronic lymphoproliferative disorders.

Diffuse large B-cell lymphoma with occult marrow involvement and a novel t(9;10)(q32;q22).

A 33-year-old man was found to have stage IV diffuse large cell lymphoma with visceral, cutaneous, and central nervous system involvement. Although examination of the posttreatment bone marrow failed to show morphologic evidence of lymphoma involvement, cytogenetic study of the marrow mononuclear cells showed the presence of a clonal abnormality t(9;10)(q32;q22), a hitherto undescribed chromosomal abnormality in diffuse large B-cell lymphoma.

Biclonal B-cell chronic lymphocytic leukemia with inv(14)(q11q32).

Cytogenetic biclonality is a rare occurrence in chronic lymphocytic leukemia. A 59-year-old man was diagnosed to have B-cell chronic lymphocytic leukemia with typical morphology and immunophenotype (CD5+, CD19+, and CD23+). However, karyotypic analysis of the small lymphocytes showed the presence of two distinct unrelated clones, including one with inv(14).

A novel t(2;3)(q31;p13) in acute myelocytic leukemia.

We report a case of acute myelocytic leukemia without maturation exhibiting a novel t(2;3)(q31;p13). Conventional cytogenetics showed the concomitant occurrence of a single metaphase with 47,XX,+8. Nevertheless, interphase cytogenetics by fluorescence in situ hybridization using a chromosome 8 alpha-satellite DNA probe showed that the percentage of cells with three hybridization signals was within the control range.

Hypoplastic myelodysplastic syndrome-a clinical, morphologic, or genetic diagnosis?

We report a middle-aged female with an 11-year history of nonprogressive pancytopenia and severely hypoplastic marrow with minimal morphologic dysplasia. A diagnosis of hypoplastic myelodysplastic syndrome (MDS) was made because of the finding of a persistent clonal abnormality, del(13)(q12q14), and the subsequent demonstration of a single Auer rod-containing blast in the peripheral blood smear. The case illustrates the problems in the differentiation between aplastic anemia and hypoplastic MDS.

Chronic lymphocytic leukemia with a novel der(8;15)(q10;q10) translocation.

A 71-year-old male was found to have chronic lymphocytic leukemia. Cytogenetic study of the leukemic lymphocytes shows a 46,XY,der(8;15)+15. The der(8;15) is a novel chromosomal abnormality in human malignancies. The resulting loss of 8p and trisomy 15q are both unusual chromosomal changes in chronic lymphocytic leukemia.

Acute myeloid leukemia with concomitant trisomies 4 and 10: a distinctive form of myeloid leukemia?

The occurrence of trisomy 4 or trisomy 10 as the sole chromosomal abnormality in acute myeloid leukemia (AML) is very rare, the reported frequency being less than 1%. We describe two cases of AML-M2 with concomitant trisomy 4 and trisomy 10, a hitherto undescribed phenomenon. They showed two unusual features, including immunoreactivity for CD56 and a short-lived but rapidly progressive myelodysplastic phase preceding the appearance of frank leukemia. These findings raise the possibility that AML with concommitant trisomy 4 and trisomy 10 may constitute a distinctive subtype of AML.

Precursor T-lymphoblastic leukemia with a novel t(1;22)(p34;q13).

A 37-year-old woman that presented with cervical lymphadenopathy and leukocytosis was found to have precursor T-lymphoblastic leukemia (T-ALL). Cytogenetic study of the leukemic cells showed a 46,XX, t(1;22)(p34;q13) karyotype. The t(1;22)(p34;q13) is a novel chromosomal abnormality in human malignancies and is probably a variant form of the t(1;14)(p34;q11) found in precursor T-ALL.

Deletion of Xq23 is a recurrent karyotypic abnormality in acute myeloid leukemia.

Deletion of chromosome Xq23 has been reported in a number of solid tumors, including soft tissue sarcoma, malignant melanoma, astrocytoma, and adenocarcinoma. The deleted Xq often occurs in a setting of very complex karyotypic changes. A similar abnormality has also been described in rare cases of acute myeloid leukemia (AML) but in no other hematologic malignancies. In this study, we report the occurrence of del(X)(q23) in two cases of AML.

Cytogenetic triclonality in T-cell acute lymphoblastic leukemia: a conventional and molecular cytogenetic study.

Cytogenetically-unrelated clones are infrequently seen in hematologic malignancies, and are particularly uncommon in acute lymphoblastic leukemia. We report a case of T-cell acute lymphoblastic leukemia with L2 morphology which demonstrated three cytogenetically distinct clones: 46,XY,t(2;9)(p21;q34)/46,XY,del(6)(q21q23)/47,XX,+8. Interphase cytogenetic analysis by fluorescence in situ hybridization (FISH) confirmed the presence of trisomy 8 in a significant proportion of lymphoblasts, while reverse transcription-polymerase chain reaction (RT-PCR) did not show the presence of BCR/ABL fusion. This is the first report describing the occurrence of cytogenetic triclonality in de novo T-cell acute lymphoblastic leukemia.

Cytogenetic divergence of the same blastic clone in transformed chronic granulocytic leukemia: no effect on morphologic and immunologic features.

A 19-year-old man with Ph-positive chronic granulocytic leukemia developed lymphoblastic transformation. Cytogenetic evolution was observed, with an abnormal clone showing i(17q) together with the t(9;22). Chronic phase of the chronic granulocytic leukemia were re-established with systemic chemotherapy, which also led to disappearance of the clone with i(17q). However, the acute lymphoblastic leukemia relapsed after 6 weeks, with the emergence of a phenotypically and genetically identical but cytogenetically distinctive clone. Our findings suggest that cytogenetic evolution in transformed chronic granulocytic leukemia reflects only the instability of the blastic clones, and may not determine its phenotypic differentiation.

Translocation(8;20;21)(q22;q13;q22) in acute myeloblastic leukemia with maturation: a variant form of t(8;21).

A 39-year-old man was diagnosed as having acute myeloblastic leukemia with maturation (AML-M2). Cytogenetic studies revealed 45,X,-Y,t(8;20)(q22;q13)[21]/46,XY[3]. Molecular analysis of the marrow mononuclear cells by reverse transcription-polymerase chain reaction with nested AML1 and ETO primers showed amplification of the AML1/ETO fusion transcript, thus confirming that the chromosomal aberration was in fact a masked t(8;21), i.e., variant t(8;20;21)(q22;q13;q22).

BCR/ABL translocation in adult acute lymphoblastic leukemia: a comparison of conventional and interphase cytogenetic studies.

Twenty-four adult Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied for the BCR/ABL translocation using both conventional cytogenetics and fluorescence in situ hybridization (FISH). Eight (33%) patients had the translocation as shown by FISH and all were B-lineage ALL (8/19, 42%). Conventional cytogenetics revealed a t(9;22)(q34;q11) in six of them, but was either unsuccessful, or not done in the other two. Seven of the eight positive cases (88%) showed a breakpoint at the minor breakpoint cluster region (m-BCR), which was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). To conclude, the frequency of BCR/ABL translocation in Chinese patients with de novo ALL is comparable to patients in the Western hemisphere, in contrast to a previous report. The predominance of m-BCR/ABL fusion among these Chinese patients with BCR/ABL translocation is also similar to patients in the Western population. Fluorescence in situ hybridization is a sensitive, specific and relatively simple technique for demonstrating this important unfavorable prognostic marker in ALL, even in a routine service laboratory setting.

Translocation (12;17)(q13;q23) in de novo acute myeloid leukemia with trilineage myelodysplasia.

12q13 abnormalities have been reported to be associated with a variety of benign and malignant solid tumors. Recently, they have been shown to be a nonrandom karyotypic change in acute myeloid leukemia. We report a case of de novo acute myeloid leukemia with trilineage myelodysplasia showing t(12;17)(q13;q23) as the sole chromosomal abnormality. A review of the literature indicates that 12q13 translocation in acute myeloid leukemia is often associated with concomitant dysmyelopoietic changes. There is also evidence to suggest that 12q13 translocation occurs more frequently in acute myeloid leukemia with a prior history of mutagenic exposure or karyotypic indicators of secondary leukemia.