Fibrin accelerates the activation of plasminogen catalyzed by tissue- type plasminogen activator much stronger than fibrinogen. Detailed studies showed that (part of) this rate-enhancing effect of fibrin is brought about by two sites in the fibrin molecule: one in A alpha-(148- 160) and one in the gamma-chain stretch 311–379 (also known as FCB-5). During the fibrinogen-to-fibrin conversion, A alpha-(148–160) appears to become accessible, because a monoclonal antibody against synthetic A alpha-(148–160) reacts with fibrin, but not with fibrinogen. Because a similar situation may exist for (at least parts of) FCB-5, we have prepared a monoclonal antibody against a part (ie, gamma-[312–324]) of FCB-5, and found that this is fibrin-specific and does not bind fibrinogen. We conclude that gamma-(312–324) is hidden in fibrinogen and is exposed by the formation of fibrin.
It was shown that the Ph1 is indeed an independent risk factor in childhood relapsed ALL. There are striking similarities between these patients and children at initial diagnosis, as well as adult patients. Therefore, it is highly suggestive that the Ph1 is also an independent risk factor under all of these circumstances.
Although the Philadelphia chromosome (Ph1) has been identified as an adverse prognostic factor in acute lymphoblastic leukemia (ALL), little is known about the incidence and clinical course of relapsed Ph1- positive ALL in children. The incidence was determined by screening of 170 consecutive children with first bone marrow relapse of ALL using the reverse transcriptase-polymerase chain reaction (RT-PCR) and comparison, with cytogenetic analysis. Among these 170 children, 20 (12%) were found to be BCR-ABL-positive, representing a rate that is about three times higher than that reported for newly diagnosed ALL. Ten of the cases were identified by RT-PCR only. In none of the 21 patients with T-cell immunophenotypes could an expression of the BCR- ABL mRNA be detected. BCR-ABL positivity was associated with a significantly shorter duration of first remission (P = .0086) and higher white blood cell (P = .0157) and blast cell counts (P = .0304) at relapse diagnosis. All patients were treated according to the ALL- REZ BFM 87 and 90 relapse trials of the BFM Relapse Study Group. The intensive multiagent chemotherapy induced a second complete remission in only 60% of children with BCR-ABL-positive ALL compared with in 91% of those without BCR-ABL expression (P = .0023). The prognosis of BCR- ABL-positive ALL in children is poor, with a probability of event-free survival at 2 years of 8% versus 50% in those without BCR-ABL mRNA or cytogenetic analysis should become part of the routine diagnostic panel for children with newly diagnosed ALL and is fundamental for children presenting with an early bone marrow relapse.
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