BackgroundLymphoid neoplasm with 18q21.3/BCL2 and 8q24/MYC translocation to immunoglobulin (IG) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome. Design and MethodsTo clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia. ResultsDual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia (p=0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L. The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) (p=0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13). ConclusionsDual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.

Early in cardiogenesis, heart primordia are brought together at the midline and fuse with each other progressively caudally-- this results in the formation of the primitive tubular heart which begins beating spontaneously at the middle period of the 9-somite developmental stage in the chick embryo. However, in these very early stages of development, the myocardial cells are small and technically difficult to impale with microelectrodes; thus electrophysiological studies on the very early embryonic heart are rare. Recently, potential sensitive dye-related absorption signals have provided a new method for monitoring spontaneous action potential activity in the early embryonic heart. This technique is based on the observation that changes in potential across membrane(s) stained with certain voltage-sensitive dyes are accompanied by changes in their optical properties (absorption, fluorescence, and/or birefringence). Using absorption signals, we have already demonstrated in embryonic pre-beating chick heart in the 7-8-somite stages, the occurrence of action potential activity, development of pacemaker potential and cardiac rhythm generation. With this method, originally introduced to record neuronal activity in invertebrate ganglia, many cells or portions of the preparation can be monitored simultaneously. Accordingly we have expanded the optical recording apparatus to monitor simultaneously spontaneous action potentials from five portions of an early embryonic heart, and report here experiments carried out on the embryonic hearts of chicks (white Leghorn) at the 7-11-somite developmental stages, corresponding to 25-35 h of incubation. The hearts attached to the embryo were stained with a merocyanine-rhodamine dye (NK2761) as a potentiometric probe. This dye is analogue of Dye XVII or Dye XXIII.

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Single ventricle cells were dissociated from the hearts of two-, three-, four- or seven-day-old chick embryos, and were maintained in vitro for an additional 6 to 28 hr. Rounded 13 to 18 micron cells with input capacitance of 5 to 10 pF were selected for analysis of fast sodium current (INa). Voltage command protocols designed to investigate the magnitude, voltage dependence, and kinetics of INa were applied with patch electrodes in the whole-cell clamp configuration. INa was present in over half of the 2d, and all 3d, 4d and 7d cells selected. The current showed no systematic differences in activation kinetics, voltage dependence, or tetrodotoxin (TTX) sensitivity with age or culture conditions. Between the 2d and 7d stages, the rate of current inactivation doubled and channel density increased about eightfold. At all stages tested, INa was blocked by TTX at a half-effective concentration of 0.5 to 1.0 nM. We conclude that the lack of Na dependence of the action potential upstroke on the second day of development results from the relatively depolarized level of the diastolic potential, and failure to activate the small available excitatory Na current. The change from Ca to Na dependence of the upstroke during the third to the seventh day of incubation results partly from the negative shift of the diastolic potential during this period, and in part from the increase in available Na conductance.

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