MLL/AF-1p Fusion in Therapy-Related Early Pre-B Acute Lymphoblastic Leukemia with t(1;11)(p32;q23) Translocation Developing in the Relapse Phase of Acute Promyelocytic Leukemia

2003 ◽  
Vol 78 (5) ◽  
pp. 439-442 ◽  
Author(s):  
Takayuki Tsujioka ◽  
Hideho Wada ◽  
Shunji Yamamori ◽  
Takemi Otsuki ◽  
Sinichiro Suemori ◽  
...  
1972 ◽  
Vol 27 (03) ◽  
pp. 516-522
Author(s):  
D. Green

SummaryFactor VIII levels are usually elevated in patients with leukemia, and recently markedly increased levels of factor VIII were described during the relapses of acute lymphoblastic leukemia in a boy with previously documented hemophilia. In this paper we describe a young man with severe classical hemophilia who developed acute promyelocytic leukemia. In contrast to the findings noted above, infused factor VIII in this patient rapidly disappeared, with a half-life of only 4-8 h (expected: 12 h). In addition, the half-life of fibrinogen was 20 h (expected: 72 h), there was marked thrombocytopenia, and decreased levels of factor V. It is suggested that the rapid consumption of factor VIII is consistent with the syndrome of “consumption coagulopathy” which was present as a complication of his acute promyelocytic leukemia.


Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5080-5083 ◽  
Author(s):  
Marie-Chantal Ethier ◽  
Esther Blanco ◽  
Thomas Lehrnbecher ◽  
Lillian Sung

Abstract Treatment-related mortality (TRM) is important in acute lymphoblastic leukemia and acute myeloid leukemia (AML); however, little is known about how TRM is defined across trials. Two major problems are related to what constitutes treatment versus disease-related cause of death and to TRM attribution (for example, death because of infection or hemorrhage). To address the former, we conducted a systematic review of randomized therapeutic pediatric acute leukemia and adult/pediatric acute promyelocytic leukemia trials and any study type focused on TRM in pediatric acute leukemia. We described definitions used for TRM. Sixty-six studies were included. Few therapeutic pediatric acute lymphoblastic leukemia studies (2/32, 6.3%) provided definitions for TRM, whereas more therapeutic pediatric AML studies (6/9, 66.7%) provided definitions. There was great heterogeneity in TRM classification. The authors of most studies relied on deaths during induction or in remission to delineate whether a death was TRM. However, 44.4% of therapeutic AML studies used death within a specific time frame to delineate TRM. We suggest that a consistent approach to defining and determining attribution for TRM in acute leukemia is an important future goal. Harmonization of definitions across the age spectrum would allow comparisons between pediatric and adult studies.


1967 ◽  
Vol 53 (6) ◽  
pp. 541-549
Author(s):  
Antonio Girolami

The behavior of factor V activity (proaccelerin) was investigated in 94 patients with acute and chronic leukemia. In acute myeloblastic and chronic myeloid leukemia normal or low levels of factor V were usually found. On the contrary in acute lymphoblastic and chronic lymphocytic leukemia normal or high levels were frequently observed. In ten patients (4 cases with acute myeloblastic leukemia, 5 cases with chronic myeloid leukemia and 1 case with acute lymphoblastic leukemia) there were markedly decreased levels of proaccelerin (less than 40%). In two patients with acute promyelocytic leukemia normal or elevated factor V activity was found. The significance of these variations in proaccelerin levels observed in leukemia is discussed.


Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 1993-2002 ◽  
Author(s):  
Tsila Zuckerman ◽  
Chezi Ganzel ◽  
Martin S. Tallman ◽  
Jacob M. Rowe

Abstract Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. Whereas clinical trials form the backbone for the management of acute leukemia, emergent clinical situations, predictable or not, are common and do not readily lend themselves to clinical trial evaluation. Furthermore, practice guidelines are often lacking. Not only are prospective trials impractical because of the emergent nature of the issue at hand, but clinicians are often reluctant to randomize such patients. Extensive practical experience is crucial and, even if there is no consensus, management of such emergencies should be guided by an understanding of the underlying pathophysiologic mechanisms.


Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1802-1810 ◽  
Author(s):  
KS Chang ◽  
G Wang ◽  
EJ Freireich ◽  
M Daly ◽  
SL Naylor ◽  
...  

Abstract Since the translocation breakpoint t(15;17) (q22;q21) in acute promyelocytic leukemia (APL) occurs within the retinoic acid receptor- alpha (RARA) gene, the expression of many genes normally regulated by RARA may be affected by this translocation. To identify genes that may be aberrantly expressed in APL, a subtraction cDNA library of an APL patient with t(15;17) was constructed. A cDNA, pRD1, specifically expressed in APL was identified. DNA sequence analysis of pRD1 showed that this gene is similar to the DNA sequence of annexin VIII, a gene which encodes a vascular anticoagulant. The annexin VIII gene was assigned to chromosome 10, which indicates that specific expression of this gene in APL is not directly involved in the t(15;17) breakpoint region. We have analyzed the expression of annexin VIII gene in nine t(15;17)-positive APL patients and one APL patient with a chromosome 17q-abnormality. We found that all APL samples expressed high levels of the annexin VIII gene. Expression of the annexin VIII gene in all other leukemias, including acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphoblastic leukemia, was undetectable, except in one patient with acute myelogenous leukemia in which a very low level of expression was detected. Annexin VIII is highly expressed in the APL cell line, NB4. Its expression was significantly reduced after 8 hours of all-trans retinoic acid (ATRA) treatment, whereas the expression of RARA increased several-fold within 4 hours postinduction. Thus, increased expression of RARA preceded the downregulation of annexin VIII after ATRA induction, suggesting an inverse relationship between RARA and annexin VIII expression. Since increased expression of the fusion transcript was seen after ATRA induction and an APL without a t(15;17) translocation expressed high levels of annexin VIII, it appears that increased expression of annexin VIII in APL is not related to the fusion transcript. Therefore, dysregulation of the RARA gene may be related to the overexpression of annexin VIII in APL.


Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1802-1810 ◽  
Author(s):  
KS Chang ◽  
G Wang ◽  
EJ Freireich ◽  
M Daly ◽  
SL Naylor ◽  
...  

Since the translocation breakpoint t(15;17) (q22;q21) in acute promyelocytic leukemia (APL) occurs within the retinoic acid receptor- alpha (RARA) gene, the expression of many genes normally regulated by RARA may be affected by this translocation. To identify genes that may be aberrantly expressed in APL, a subtraction cDNA library of an APL patient with t(15;17) was constructed. A cDNA, pRD1, specifically expressed in APL was identified. DNA sequence analysis of pRD1 showed that this gene is similar to the DNA sequence of annexin VIII, a gene which encodes a vascular anticoagulant. The annexin VIII gene was assigned to chromosome 10, which indicates that specific expression of this gene in APL is not directly involved in the t(15;17) breakpoint region. We have analyzed the expression of annexin VIII gene in nine t(15;17)-positive APL patients and one APL patient with a chromosome 17q-abnormality. We found that all APL samples expressed high levels of the annexin VIII gene. Expression of the annexin VIII gene in all other leukemias, including acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphoblastic leukemia, was undetectable, except in one patient with acute myelogenous leukemia in which a very low level of expression was detected. Annexin VIII is highly expressed in the APL cell line, NB4. Its expression was significantly reduced after 8 hours of all-trans retinoic acid (ATRA) treatment, whereas the expression of RARA increased several-fold within 4 hours postinduction. Thus, increased expression of RARA preceded the downregulation of annexin VIII after ATRA induction, suggesting an inverse relationship between RARA and annexin VIII expression. Since increased expression of the fusion transcript was seen after ATRA induction and an APL without a t(15;17) translocation expressed high levels of annexin VIII, it appears that increased expression of annexin VIII in APL is not related to the fusion transcript. Therefore, dysregulation of the RARA gene may be related to the overexpression of annexin VIII in APL.


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