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Acute promyelocytic leukemia—mobile and infiltrative
Leukemia Research 31 (2007) 5–7
Guest editorial
Acute promyelocytic leukemia—mobile and infiltrative
Since adhesion receptors influence cell–cell interactions and interaction of cells with their stromal and matrix microenvironment, it is likely that adhesion receptors expressed by acute myeloid leukemia (AML) cells play a role in their marrow egress and infiltration into other tissue sites [1]. In this issue of Leukemia Research, Moscinski and colleagues report one of the largest analyses of 2 integrin adhesion receptors in AML [2]. Only alpha chain expression (CD11a, b, and c) was analyzed. Expression of the beta chain (CD18) was not measured. 339 cases were examined, and levels of CD11b and CD11c were correlated with increased white cell count without correlation to leukemia subtype based on the FAB classification. The other major finding was that 93% of acute promyelocytic leukemia (APML) cases (defined by cytogenetic or molecular criteria) lacked 2 integrin expression whereas only 11% of non-M3 samples lacked such expression. Furthermore, after all-trans retinoic acid (ATRA) exposure, 2 integrin expression on APML blood samples was detectable. Based on these findings, the authors propose that a panel of 2 integrins be included in the flow cytometry panel utilized in AML diagnosis. If each of these antigens (CD11a, 11b, and 11c) were negative, ATRA therapy could be started prior to availability of definitive cytogenetic or PCR results in suspected cases of APML. It remains unclear how much addition of these antigens to the usual APML profile (CD34- /CD33+/CD13+//HLA-DR negative) [3] would aid in distinguishing APML from other AML subtypes. This immune phenotype coupled with morphologic findings of bilobed nuclear shape, azurophilic granules, and myeloperoxidase positivity with Auer rods is usually sufficient to make a diagnosis of APML, and the role of 2 expression in contributing to this ability would need to be validated in a larger group of APML patients [4]. Increasing sensitivity of an immune profile might aid the ability to diagnose hypogranular or microgranular variants before t (15;17) (p22; q12-21) is detected by banding cytogenetics or before PML/RAR-␣ expression by polymerase chain reaction is known. This could increase comfort levels with starting ATRA therapy in smaller centers where PCR or FISH are not available on site. In most centers where AML is 0145-2126/$ – see front matter © 2006 Published by Elsevier Ltd. doi:10.1016/j.leukres.2006.05.025
treated, however, FISH results for the t (15; 17) translocation could be available in 48 h if the clinical diagnosis is suspected [4]. Early diagnosis is probably of importance since ATRA can more quickly reverse the coagulation aberrancies seen in APML than does chemotherapy [5], but the incidence of early death from thromboembolic or hemorrhagic disease has not decreased in the ATRA era despite better disease free and overall survival rates [6]. Whether the availability of 2 expression profiles would prevent misdiagnosis of APML and unnecessary use of ATRA is also uncertain. One large trial of APML has reported upon the number of patients enrolled who were initially misdiagnosed by morphology (23 out of 401) [7], but cytogenetic or PCR results have not been utilized in this determination in most studies reported upon to date [7]. In this work, blasts from marrow were analyzed at diagnosis, and expression of CD11a, CD11b, and CD11c correlated with WBC values at presentation. It is unknown whether the expression of 2 integrins on circulating blasts might be altered by the process of marrow egress. The presence of 2 intergrins does, however, perhaps indicate a propensity for egress through endothelial barriers, thus explaining higher blood counts in these patients [8]. This group also found that CD117 correlated with increased white count. This is unexpected in that mobilized progenitors express less CD117 than their marrow counterparts and the SCF/c-kit axis is thought to play a role in cell retention in marrow microenvironmental niches. [9,10]. Another speculation put forward in the manuscript by Moscinski is that upregulation of the 2 integrins during ATRA therapy is linked to the hyperleukocytosis which typifies the ATRA syndrome. The ATRA syndrome occurs in 26% of APML cases during induction with ATRA alone but is not seen during maintenance therapy [11]. This syndrome, characterized by unexplained fever, fluid retention, pleuropericardial, effusions, and pulmonary infiltrates, can also be seen with arsenic trioxide therapy [12]. The ATRA syndrome is associated with leukocytosis [13], and early addition of chemotherapy to ATRA can reduce the incidence of ATRA syndrome. Autopsy series show interstitial infiltrates of maturing myeloid cells with patent alveoli, unlike
6
Guest editorial / Leukemia Research 31 (2007) 5–7
the blast replacement of alveolar space in hyperleukocytosis with other AML subtypes. The ATRA syndrome involves cell trafficking to extramedullary locations and is probably mediated both by chemokines [14] and adhesion receptors. It is thought that ATRA promotes adherence of differentiated APML cells to vascular endothelium and upregulates MMP-2, MMP-9, and urokinase, thus promoting invasion of the extracellular matrix [15]. Other investigators have found roles for ICAM1 in extravasation of APML cells [16], and in the NB4 promyelocytic cell line, increased adhesion to Matrigel and migration of ATRA-exposed APML cells was noted in conjunction with increased 2 integrin expression (CD11a and CD11b) but not with change in 1 integrin expression. [17] No effects on MMP-9 and MMP-2 were noted in other studies [17]. Other groups have also confirmed that in fresh APML blast cells, CD11a, CD11b, CD11c, and CD54 expression are lower than in AML blasts of other subtypes [18]. Thomas et al. [19] found that 1 integrin, CD54, and CD56 expression were higher in APML than in other subtypes but decreased with differentiation. No difference in adhesion to extracellular matrix proteins was found in the presence of ATRA. β2 integrins may be initially utilized by ATRA-treated cells to transmigrate activated endothelium, and ATRA has been found to increase E-selectin mediated rolling [8]. In addition to alteration in chemokine and adhesion receptor expression in APML, ATRA can exaggerate actin responses to inflammatory mediators which may also play a role in the ATRA syndrome [20]. ATRA may also affect the endothelium itself, thereby altering leukemic cell egress capabilities and attachment and lodgement in extramedullary capillary beds. Dexamethasone, for example, while improving the ATRA syndrome, does not affect differentiaton, normalization of PML-nuclear bodies, or the anti-proliferatve effect of retinoids, suggesting that it mediates endothelial cell changes or changes in soluble chemokine or cytokine mediators of the syndrome [21]. The ability of APML cells to modulate their adhesion receptors with differentiation and their ability to traverse endothelium is possibly related to extramedullary disease noted with APML, especially in patients who have developed the ATRA syndrome during induction [22]. Sweet’s syndrome is also seen with APML during ATRA therapy with differentiated APML cells infiltrating skin [23]. CD56 expression which has been correlated with extramedullary disease has been found to be a marker of poor prognosis in APML treated with ATRA and chemotherapy [24]. The APML samples in Moscinski’s study were all obtained from peripheral blood during ATRA induction as frequent marrow sampling is not routinely done during induction Expression of adhesion receptors during in vivo ATRA exposure could be followed in only 7/27 patients; none of whom developed the ATRA syndrome and none of whom received other cytotoxic chemotherapy. This analysis is complicated by the fact that the mononuclear fraction analyzed
contained not only blast cells but differentiating cells. CD11c preceded CD11b and CD11a expression during ATRA therapy. Since these antigens are detected on cells already in circulation, it is uncertain to what extent they are involved in the leukocytosis which often accompanies ATRA syndrome. It is also uncertain to what extent they contribute to adherence of differentiated APML cells to vascular endothelium in response to chemokine gradients. It thus remains unclear whether 2 expression is involved in the ATRA syndrome or is merely a marker of the differentiation which occurs with ATRA therapy and is key to its therapeutic effectiveness in APML. Continued analysis of the role that adhesion receptors play in clinical characteristics of APML will be of importance as attempts are made to enhance diagnostic parameters and better understand hyperleukocytotic syndromes and propensity for extramedullary disease. While prophylactic or early therapeutic dexamethasone may decrease the incidence and severity of this syndrome, it remains an important risk of ATRA therapy [25]. Studies such as that of Moscinski further that understanding and reveal missing pieces of knowledge in understanding the trafficking of AML, and in particular, APML cells.
References [1] Vila L, Thomas X, Campos L, sabido O, Archimbaud E. Expression of VLA molecules on acute leukemia cells: relationship with disease characteristics. Exp Hematol 1995;23:514–8. [2] Wu JJ, Cantor A, Moscinski LC. 2 Integrins are characteristically absent in acute promyelocytic leukemia and rapidly upregulated in vivo upon differentiation with all trans retinoic acid. Leuk Res 2007;31(1):49–57. [3] World Health Organization Classifcation of Tumours. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001. [4] Horton Y, Ford A, MacKie MJ, Johnson PR. Rapid detection of BCR/ABL and PML/RARA using fluorescence in situ hybridization in cytospin preparations. Clin Lab Haematol 2000;22:97–102. [5] Tallman MS, Lebebvre P, Baine RM, Shoji M, Cohen I, Green D, et al. Effects of all-transretinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2004;2:1341– 50. [6] Tallman MS, Rowe JM. Long-term follow-up and potential for cure in acute promyelocytic leukemia. Best Pract Res Clin Haematol 2003;156:535–43. [7] Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia; long-term outcome and prognostic factor analysis form the North American Intergroup protocol. Blood 2002;100:4298–302. [8] Brown DC, Tsuji H, Larson RS. All-trans retinoic acid regulates adhesion mechanism and transmigration of the actue promyelocytic leukaemia cell line NB-4 under physiologic flow. Br J Haematol 1999;107:86–98. [9] Bendall LJ, Makrnyikola V, Hutchinson A, Bianchi AC, Bradstock KF, Gottlieb DJ. Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals. Leukemia 1998;12:1375–82.
Guest editorial / Leukemia Research 31 (2007) 5–7 [10] Kroger N, Zeller W, Hassan HT, Dierlamm J, Zander AR. Difference betweeen expression of adhesion molecules on CD34+ cells from bone marrow and G-CSF-stimulated peripheral blood. Stem Cells 1998;16:49–53. [11] Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 2000;95:90–5. [12] Camacho LH, Soignet SL, Chanel S, Ho R, Heller G, Scheinberg DA, et al. Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide. J Clin Oncol 2000;18:2620–5. [13] Tallman MS. Differentiating therapy in acute myeloid leukemia. Leukemia 1996;10(Suppl. 2):s33–8. [14] Hsu HC, Tsai WH, Chen PG, Hsu ML, Ho CK, Wang SY. In vitro effect of granulocyte-colony stimulating factor and all-trans retinoid acid on the expression of inflammatory cytokines and adhesion molecules in acute promyelocytic leukemic cells. Eur J Haematol 1999;63: 11–8. [15] Shibakura M, Nilya K, Kiguchi T, Shinagawa K, Ishimaru F, Ikeda K, et al. Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells. Br J Haematol 2002;118:425–91. [16] Mustjoki S, Alitalo R, Elonen E, Carpen O, Gahmberg CG, Vaheri A. Intercellular adhesion molecule-1 in extravasation of normal mononuclear and leukaemia cells. Br J Hematol 2001;113:989–1000. [17] Zang C, Liu H, Ries C, Ismair MG, Petrides PE. Enhanced migration of the acute promyelocytic leukemia cell line NB4 under in vitro conditions during short-term all-trans-retinoic acid treatment. J Cancer Res Clin Oncol 2000;126:133–40. [18] DiNoto RL, Pardo C, Schiavone EM, Ferrara F, Manzo C, Vacca C, et al. All-trans retinoic acid (ATRA) and the regulation of adhesion molecules in acute myeloid leukemia. Leuk Lymphoma 1996;21:201–9. [19] Thomas X, Anglaret B, Campos L, Thiebaut A, Sabido G, Bailly J, et al. Expression of beta1-interrins and pseudo-immmunoglobulins on
[20]
[21]
[22]
[23]
[24]
[25]
7
acute promyelocytic leukemia cells and its modifications during in vitro differentiation. Leuk Res 1998;22:61–8. Sham RL, Phatak PD, Belanger KA, Braggins C, Packman CH. Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid. Leuk Res 1995;19:505–11. De Ridder MC, van der Plas AJ, Erpelinck-Verschueren CA, Lowenberg B, Jansen JR. Dexamethasone does not counteract the response of acute promyelocytic leukemic cells to all-trans retinoic acid. Br J Haematol 1999;106:107–10. Ko BS, Tang JL, Chen YC, Yao M, Wang CH, Shen MC, et al. Extramedullary relapse after all-transretinoic acid treatment in acute promyelocytic leukemia–the occurrence of retinoic acid syndrome is a risk factor. Leukemia 1999;13:1406–8. Arun B, Berberian B, Azumi N, Frankel SR, Luksenburg N, Freter C. Sweet’s syndrome during treatment with all-transretinoic acid in a patient with acute promyelocytic leukemia. Leuk Lymphoma 1998;31:613–5. Ferrara F, Morabito F, Martion B, Specchia G, Liso V, Mobile F, et al. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy. J Clin Oncol 2000;18:1295– 300. Tallman MS. Retinoic acid syndrome: a problem of the past? Leukemia 2002;16:160–1.
Jane L. Liesveld James P. Wilmot Cancer Center, 601 Elmwood Avenue Box 704, Rochester, NY 14642, United States Tel.: +1 585 275 4099; fax: +1 585 273 1051. E-mail address: jane [email protected] Available online 15 September 2006
Guest editorial
Acute promyelocytic leukemia—mobile and infiltrative
Since adhesion receptors influence cell–cell interactions and interaction of cells with their stromal and matrix microenvironment, it is likely that adhesion receptors expressed by acute myeloid leukemia (AML) cells play a role in their marrow egress and infiltration into other tissue sites [1]. In this issue of Leukemia Research, Moscinski and colleagues report one of the largest analyses of 2 integrin adhesion receptors in AML [2]. Only alpha chain expression (CD11a, b, and c) was analyzed. Expression of the beta chain (CD18) was not measured. 339 cases were examined, and levels of CD11b and CD11c were correlated with increased white cell count without correlation to leukemia subtype based on the FAB classification. The other major finding was that 93% of acute promyelocytic leukemia (APML) cases (defined by cytogenetic or molecular criteria) lacked 2 integrin expression whereas only 11% of non-M3 samples lacked such expression. Furthermore, after all-trans retinoic acid (ATRA) exposure, 2 integrin expression on APML blood samples was detectable. Based on these findings, the authors propose that a panel of 2 integrins be included in the flow cytometry panel utilized in AML diagnosis. If each of these antigens (CD11a, 11b, and 11c) were negative, ATRA therapy could be started prior to availability of definitive cytogenetic or PCR results in suspected cases of APML. It remains unclear how much addition of these antigens to the usual APML profile (CD34- /CD33+/CD13+//HLA-DR negative) [3] would aid in distinguishing APML from other AML subtypes. This immune phenotype coupled with morphologic findings of bilobed nuclear shape, azurophilic granules, and myeloperoxidase positivity with Auer rods is usually sufficient to make a diagnosis of APML, and the role of 2 expression in contributing to this ability would need to be validated in a larger group of APML patients [4]. Increasing sensitivity of an immune profile might aid the ability to diagnose hypogranular or microgranular variants before t (15;17) (p22; q12-21) is detected by banding cytogenetics or before PML/RAR-␣ expression by polymerase chain reaction is known. This could increase comfort levels with starting ATRA therapy in smaller centers where PCR or FISH are not available on site. In most centers where AML is 0145-2126/$ – see front matter © 2006 Published by Elsevier Ltd. doi:10.1016/j.leukres.2006.05.025
treated, however, FISH results for the t (15; 17) translocation could be available in 48 h if the clinical diagnosis is suspected [4]. Early diagnosis is probably of importance since ATRA can more quickly reverse the coagulation aberrancies seen in APML than does chemotherapy [5], but the incidence of early death from thromboembolic or hemorrhagic disease has not decreased in the ATRA era despite better disease free and overall survival rates [6]. Whether the availability of 2 expression profiles would prevent misdiagnosis of APML and unnecessary use of ATRA is also uncertain. One large trial of APML has reported upon the number of patients enrolled who were initially misdiagnosed by morphology (23 out of 401) [7], but cytogenetic or PCR results have not been utilized in this determination in most studies reported upon to date [7]. In this work, blasts from marrow were analyzed at diagnosis, and expression of CD11a, CD11b, and CD11c correlated with WBC values at presentation. It is unknown whether the expression of 2 integrins on circulating blasts might be altered by the process of marrow egress. The presence of 2 intergrins does, however, perhaps indicate a propensity for egress through endothelial barriers, thus explaining higher blood counts in these patients [8]. This group also found that CD117 correlated with increased white count. This is unexpected in that mobilized progenitors express less CD117 than their marrow counterparts and the SCF/c-kit axis is thought to play a role in cell retention in marrow microenvironmental niches. [9,10]. Another speculation put forward in the manuscript by Moscinski is that upregulation of the 2 integrins during ATRA therapy is linked to the hyperleukocytosis which typifies the ATRA syndrome. The ATRA syndrome occurs in 26% of APML cases during induction with ATRA alone but is not seen during maintenance therapy [11]. This syndrome, characterized by unexplained fever, fluid retention, pleuropericardial, effusions, and pulmonary infiltrates, can also be seen with arsenic trioxide therapy [12]. The ATRA syndrome is associated with leukocytosis [13], and early addition of chemotherapy to ATRA can reduce the incidence of ATRA syndrome. Autopsy series show interstitial infiltrates of maturing myeloid cells with patent alveoli, unlike
6
Guest editorial / Leukemia Research 31 (2007) 5–7
the blast replacement of alveolar space in hyperleukocytosis with other AML subtypes. The ATRA syndrome involves cell trafficking to extramedullary locations and is probably mediated both by chemokines [14] and adhesion receptors. It is thought that ATRA promotes adherence of differentiated APML cells to vascular endothelium and upregulates MMP-2, MMP-9, and urokinase, thus promoting invasion of the extracellular matrix [15]. Other investigators have found roles for ICAM1 in extravasation of APML cells [16], and in the NB4 promyelocytic cell line, increased adhesion to Matrigel and migration of ATRA-exposed APML cells was noted in conjunction with increased 2 integrin expression (CD11a and CD11b) but not with change in 1 integrin expression. [17] No effects on MMP-9 and MMP-2 were noted in other studies [17]. Other groups have also confirmed that in fresh APML blast cells, CD11a, CD11b, CD11c, and CD54 expression are lower than in AML blasts of other subtypes [18]. Thomas et al. [19] found that 1 integrin, CD54, and CD56 expression were higher in APML than in other subtypes but decreased with differentiation. No difference in adhesion to extracellular matrix proteins was found in the presence of ATRA. β2 integrins may be initially utilized by ATRA-treated cells to transmigrate activated endothelium, and ATRA has been found to increase E-selectin mediated rolling [8]. In addition to alteration in chemokine and adhesion receptor expression in APML, ATRA can exaggerate actin responses to inflammatory mediators which may also play a role in the ATRA syndrome [20]. ATRA may also affect the endothelium itself, thereby altering leukemic cell egress capabilities and attachment and lodgement in extramedullary capillary beds. Dexamethasone, for example, while improving the ATRA syndrome, does not affect differentiaton, normalization of PML-nuclear bodies, or the anti-proliferatve effect of retinoids, suggesting that it mediates endothelial cell changes or changes in soluble chemokine or cytokine mediators of the syndrome [21]. The ability of APML cells to modulate their adhesion receptors with differentiation and their ability to traverse endothelium is possibly related to extramedullary disease noted with APML, especially in patients who have developed the ATRA syndrome during induction [22]. Sweet’s syndrome is also seen with APML during ATRA therapy with differentiated APML cells infiltrating skin [23]. CD56 expression which has been correlated with extramedullary disease has been found to be a marker of poor prognosis in APML treated with ATRA and chemotherapy [24]. The APML samples in Moscinski’s study were all obtained from peripheral blood during ATRA induction as frequent marrow sampling is not routinely done during induction Expression of adhesion receptors during in vivo ATRA exposure could be followed in only 7/27 patients; none of whom developed the ATRA syndrome and none of whom received other cytotoxic chemotherapy. This analysis is complicated by the fact that the mononuclear fraction analyzed
contained not only blast cells but differentiating cells. CD11c preceded CD11b and CD11a expression during ATRA therapy. Since these antigens are detected on cells already in circulation, it is uncertain to what extent they are involved in the leukocytosis which often accompanies ATRA syndrome. It is also uncertain to what extent they contribute to adherence of differentiated APML cells to vascular endothelium in response to chemokine gradients. It thus remains unclear whether 2 expression is involved in the ATRA syndrome or is merely a marker of the differentiation which occurs with ATRA therapy and is key to its therapeutic effectiveness in APML. Continued analysis of the role that adhesion receptors play in clinical characteristics of APML will be of importance as attempts are made to enhance diagnostic parameters and better understand hyperleukocytotic syndromes and propensity for extramedullary disease. While prophylactic or early therapeutic dexamethasone may decrease the incidence and severity of this syndrome, it remains an important risk of ATRA therapy [25]. Studies such as that of Moscinski further that understanding and reveal missing pieces of knowledge in understanding the trafficking of AML, and in particular, APML cells.
References [1] Vila L, Thomas X, Campos L, sabido O, Archimbaud E. Expression of VLA molecules on acute leukemia cells: relationship with disease characteristics. Exp Hematol 1995;23:514–8. [2] Wu JJ, Cantor A, Moscinski LC. 2 Integrins are characteristically absent in acute promyelocytic leukemia and rapidly upregulated in vivo upon differentiation with all trans retinoic acid. Leuk Res 2007;31(1):49–57. [3] World Health Organization Classifcation of Tumours. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001. [4] Horton Y, Ford A, MacKie MJ, Johnson PR. Rapid detection of BCR/ABL and PML/RARA using fluorescence in situ hybridization in cytospin preparations. Clin Lab Haematol 2000;22:97–102. [5] Tallman MS, Lebebvre P, Baine RM, Shoji M, Cohen I, Green D, et al. Effects of all-transretinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2004;2:1341– 50. [6] Tallman MS, Rowe JM. Long-term follow-up and potential for cure in acute promyelocytic leukemia. Best Pract Res Clin Haematol 2003;156:535–43. [7] Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia; long-term outcome and prognostic factor analysis form the North American Intergroup protocol. Blood 2002;100:4298–302. [8] Brown DC, Tsuji H, Larson RS. All-trans retinoic acid regulates adhesion mechanism and transmigration of the actue promyelocytic leukaemia cell line NB-4 under physiologic flow. Br J Haematol 1999;107:86–98. [9] Bendall LJ, Makrnyikola V, Hutchinson A, Bianchi AC, Bradstock KF, Gottlieb DJ. Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals. Leukemia 1998;12:1375–82.
Guest editorial / Leukemia Research 31 (2007) 5–7 [10] Kroger N, Zeller W, Hassan HT, Dierlamm J, Zander AR. Difference betweeen expression of adhesion molecules on CD34+ cells from bone marrow and G-CSF-stimulated peripheral blood. Stem Cells 1998;16:49–53. [11] Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 2000;95:90–5. [12] Camacho LH, Soignet SL, Chanel S, Ho R, Heller G, Scheinberg DA, et al. Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide. J Clin Oncol 2000;18:2620–5. [13] Tallman MS. Differentiating therapy in acute myeloid leukemia. Leukemia 1996;10(Suppl. 2):s33–8. [14] Hsu HC, Tsai WH, Chen PG, Hsu ML, Ho CK, Wang SY. In vitro effect of granulocyte-colony stimulating factor and all-trans retinoid acid on the expression of inflammatory cytokines and adhesion molecules in acute promyelocytic leukemic cells. Eur J Haematol 1999;63: 11–8. [15] Shibakura M, Nilya K, Kiguchi T, Shinagawa K, Ishimaru F, Ikeda K, et al. Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells. Br J Haematol 2002;118:425–91. [16] Mustjoki S, Alitalo R, Elonen E, Carpen O, Gahmberg CG, Vaheri A. Intercellular adhesion molecule-1 in extravasation of normal mononuclear and leukaemia cells. Br J Hematol 2001;113:989–1000. [17] Zang C, Liu H, Ries C, Ismair MG, Petrides PE. Enhanced migration of the acute promyelocytic leukemia cell line NB4 under in vitro conditions during short-term all-trans-retinoic acid treatment. J Cancer Res Clin Oncol 2000;126:133–40. [18] DiNoto RL, Pardo C, Schiavone EM, Ferrara F, Manzo C, Vacca C, et al. All-trans retinoic acid (ATRA) and the regulation of adhesion molecules in acute myeloid leukemia. Leuk Lymphoma 1996;21:201–9. [19] Thomas X, Anglaret B, Campos L, Thiebaut A, Sabido G, Bailly J, et al. Expression of beta1-interrins and pseudo-immmunoglobulins on
[20]
[21]
[22]
[23]
[24]
[25]
7
acute promyelocytic leukemia cells and its modifications during in vitro differentiation. Leuk Res 1998;22:61–8. Sham RL, Phatak PD, Belanger KA, Braggins C, Packman CH. Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid. Leuk Res 1995;19:505–11. De Ridder MC, van der Plas AJ, Erpelinck-Verschueren CA, Lowenberg B, Jansen JR. Dexamethasone does not counteract the response of acute promyelocytic leukemic cells to all-trans retinoic acid. Br J Haematol 1999;106:107–10. Ko BS, Tang JL, Chen YC, Yao M, Wang CH, Shen MC, et al. Extramedullary relapse after all-transretinoic acid treatment in acute promyelocytic leukemia–the occurrence of retinoic acid syndrome is a risk factor. Leukemia 1999;13:1406–8. Arun B, Berberian B, Azumi N, Frankel SR, Luksenburg N, Freter C. Sweet’s syndrome during treatment with all-transretinoic acid in a patient with acute promyelocytic leukemia. Leuk Lymphoma 1998;31:613–5. Ferrara F, Morabito F, Martion B, Specchia G, Liso V, Mobile F, et al. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy. J Clin Oncol 2000;18:1295– 300. Tallman MS. Retinoic acid syndrome: a problem of the past? Leukemia 2002;16:160–1.
Jane L. Liesveld James P. Wilmot Cancer Center, 601 Elmwood Avenue Box 704, Rochester, NY 14642, United States Tel.: +1 585 275 4099; fax: +1 585 273 1051. E-mail address: jane [email protected] Available online 15 September 2006