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Minimally differentiated acute myeloid leukemia (AML-M0) with extensive erythrophagocytosis and del(20)(q11) chromosome abnormality
Leukemia Research 24 (2000) 87 – 90 www.elsevier.com/locate/leukres
Case report
Minimally differentiated acute myeloid leukemia (AML-M0) with extensive erythrophagocytosis and del(20)(q11) chromosome abnormality Hiroyuki Mori a,*, Masayuki Tawara a, Yoshiharu Yoshida b, Kazutaka Kuriyama a, Kazuyuki Sugahara c, Shimeru Kamihira c, Masao Tomonaga a a
Department of Hematology, Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki Uni6ersity School of Medicine, 1 -12 -4 Sakamoto, Nagasaki 852 -8102, Japan b Department of Internal Medicine, St. Francisco Hospital, Nagasaki, Japan c Department of Laboratory Medicine, Nagasaki Uni6ersity School of Medicine, Nagasaki, Japan Received 26 April 1999; accepted 12 July 1999
Abstract We describe an 84-year-old woman who presented severe pancytopenia and 36.6% of blasts accompanied with erythrophagocytosis in the bone marrow. According to cytochemical and immunological findings, a diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was established. Cytogenetic analysis revealed del(20)(q11) which were previously reported for one case each of ALL and MDS associated with cytophagocytosis by blasts, leading us to speculate a disease entity. Interestingly, a high expression of mRNA of TNF-a was detected by RT-PCR on the bone marrow mononuclear cells. © 1999 Elsevier Science Ltd. All rights reserved. Keywords: Acute myeloid leukemia; AML-M0; Cytophagocytosis; Deletion 20q; Tumor necrosis factor-a
1. Introduction Acute myeloid leukemia (AML) associated with cytophagocytosis by blast cells usually represent differentiated phenotypes of monocyte and/or granulocyte (M4/M5) [1], and also reported in M1, M2 and M7. Cytogenetic abnormalities in AML with cytophagocytosis reported in more than two cases were t(8;16)(p11;p13) and inv(8)(p11q13) in M4/M5, and t(16;21)(p11;q22). Other chromosomal abnormalities were reported sporadically. A terminal or interstitial deletion of the long arm of chromosome 20(20q− ) is one of the common chromosome abnormalities in myeloid disorders such as myelodysplastic syndrome (MDS), myeloproliferative disorders and AML [2]. Although it is a rare cytogenetic abnormality in acute lymphocytic leukemia (ALL), a case of ALL associated * Corresponding author. Fax: +81-95-8497113.
with del(20)(q11) was reported to have a striking erythrophagocytosis by blast cells [3].We here report a case of AML-M0 showing erythrophagocytosis and del(20)(q11).
2. Case report An 84-year-old woman was admitted to another hospital because of fever with chills and skin abscess. After admission severe pancytopenia and an increased number of abnormal cells associated with erythrophagocytosis in the bone marrow were found. Five years ago, when she had a operation for cataract, mild thrombocytopenia (platelets count of 117 109/l) was pointed out but no other hematological abnormality. The infection subsided which treatment with antibiotics and granulocyte-colony stimulating factor (G-CSF). Then she was referred to our hospital for further examination. On
0145-2126/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 1 4 5 - 2 1 2 6 ( 9 9 ) 0 0 1 4 5 - 9
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H. Mori et al. / Leukemia Research 24 (1999) 87–90
physical examination, neither lymphoadenopathy nor hepatosplenomegaly was detected. Laboratory examination revealed hemoglobin 7.7 g/ dl, white blood cell count 0.6 /l with 1% blast, 0% granulocytes, 97% lymphocytes and 2% monocytes, and platelets count 33 /l. Coagulation tests were almost normal. The serum lactate dehydrogenase (LDH) level, serum and urine lysozyme were not elevated. Bone marrow aspiration revealed a mild hypocellular marrow, but megakaryocyts were preserved. Mature granulocytes were markedly decreased (1.2% of bone marrow nucleated cells), and erythroid cells were 24.8% of all nucleated cells and some of them had megaloblastoid changes. Blast cells were 36.6% in the marrow, which were highly variable in size and the morphological features, and some of them showing extensive erythrophagocytosis (Fig. 1). Mature monocytes were 0.45% of all nucleated cells. Staining for myeloperoxidase, chloroacetate esterase and butyrate esterase were all negative in the blast cells. Immunocytochmical staining and immunophenotyping by flowcytometory re-
vealed that most of the blast cells were positive for CD13, CD33 and HLA-DR, and negative for CD34, TdT, CD14,CD3, CD5, CD19, CD22, CD41, GPA, CD10 and MPO. Cytochemical and immunological findings were consistent with a diagnosis of AML-M0. On the bone marrow mononuclear cells, TCR and IgH rearrangements were not detected by PCR-SSCP (single strand conformation polymorphism). Cytogenetic analysis on the bone marrow cells showed del(20)(q11) in all metaphase analyzed, and 4/20 metaphase associated with + 21 (Fig. 2). The expression of cytokines was determined in mRNA level on the bone marrow mononuclear cells by RT-PCR. Total RNA was isolated from cell pellets by acid guanidinium thiocyanate–phenol–chloroform technique and treated by DNase. The cDNA was synthesized from 1 mg of total RNA using RNA PCR Core™ kit (Perkin-Elmer, NJ). PCR was carried out using following primers (hTNF-: Sense; 5%-ATGAGCATCGAAAGCATG-3%, Antisense; 5%TCACAGGGCAATGATCCC-3%) [4] and TaKaRa Ex Taq™ polymerase (Takara, Tokyo), and 30 cycles of amplification (95°C for 1 min, 55°C for 1 min, 72°C for 1 min). PCR products were electorophoresed on a 2% agarose gel and stained with ethidium bromide. A strong band of TNF-a was observed in patient (Fig. 3, lane 1) and thin band was identified in normal subject (lane 3). Furthermore to determine the level of TNF-a mRNA expression, a competitive PCR method using CytoXpress (Biosource International, California) for TNF- and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed. The ratio of copy number of TNF-a to GAPDH were 0.0479 in this patient and 0.0057 in normal subject (lane 3). The mRNA for FasL, IL-2 and IFN-g were not increased in this case compared with normal subjects (data not shown). Initially, because of no apparent growth of the leukemic cells and being asymptomatic, we administered only blood transfusion. As the disease progressed, the patient was treated with low dose cytosine arabinoside and aclarubicin, but it was not possible to have sufficient therapeutic effect. She died of pneumonia 6 months after the diagnosis.
3. Discussion
Fig. 1. Blasts from bone marrow of the patient. (A) Blasts showed the striking variability in morphology. Some had high nuclear/cytoplasmic ratio, others had low. Most of phagocyting blast cells showed scanty cytoplasm and no guranules (May-Grunwald Giemsa stain). (B) CD33 positive blasts by immunocytochemistory stain.
Cytochemical and immunological examinations did not reveal the features of differentiation towards either monocytes or granulocytes. According to the formulation of FAB classification system [5], we considered this case as minimally differentiated acute myeloid leukemia (AML-M0). It was reported that cytophagocytosis by leukemic blasts was observed in approximately 1% of all types of AML patients, and relatively frequent in monocytic types (M4, M5), but also seen in M1, M2
H. Mori et al. / Leukemia Research 24 (1999) 87–90
89
Fig. 2. Representative G-banded karyotype obtained from bone marrow. Arrow indicates deleted chromosome.
and M7. To our knowledge, there is no previous report of MO type AML presenting cytophagocytosis. This case seemed to be distinct from typical MO in terms of cell morphology and negativity of CD34 [6]. Moreover, we could not exclude completely a possibility of preceding MDS. Although the pathogenesis of phagocytosis is still unclear, some reports suggest association of several kinds of cytokines [7,8]. In our case, although the expression of mRNA of IL-2 and IFN-g were comparable with normal bone marrow, the expression of mRNA of TNF-a was greatly increased as detected by semi-quantitative RT-PCR on the bone marrow mononuclear cells. Though the origin of cells expressing TNF-a was unclear, it is likely that TNF-a contributed to the clinical features of cytophagocytosis in this case. In the previous reports, TNF-a was constitutively secreted by some AML cells, and acted as a growth stimulator of leukemic cells on some conditions [9]. TNF-a can also activate monocytes and enhance erythrophagocytosis [10]. It is known that a del(20q) is one of the common chromosome abnormalities in MDS, myeloproliferative disorders and AML, and the spectrum of these diseases led us to speculate that long arm of chromosome 20 represents the site of a tumor suppressor gene [2]. It was previously reported as a rare event that an ALL case associated with del(20)(q11) showed striking erythrophagocytosis by blast cells [3]. Furthermore, a case of MDS (refractory anemia with excess of blasts in transformation; RAEBt) who presented erythrophagocytosis had also del(20)(q12q13) abnormality [10]. Long arm of chromosome 20 is known to have several candidate tumor suppressor genes including hematopoietic cell kinase (hck) [11]; some functional genes that con-
Fig. 3. RT-PCR analysis of human TNF-a mRNA expression in marrow cells. Expression of TNF-a (upper column) and b-actin (lower column). Lane 1 represents this patient and lanes 2 and 3 represent normal subjects.
tribute to pathogenesis of those patients with cytophagocytosis might also exist in this region. Thus, our observation seems likely to suggest a disease entity which is characterized by cytophagocytosis by leukemic blasts and chromosome abnormality of 20q [12]. The 8p11 anomaly in M4/M5 is predominantly associated with cytophagocytosis, and also t(10;17)(p13;p12) [13] and t(16;21)(p11;q22) [14] were reported in M7 in relation to phagocytic properties. We emphasize the significance of 20q anomaly in cytophagocytosis because it appears to occur overriding cell lineages and clinical categories of leukemia.
References [1] Liso V, Specchia G, Capalbo S, Laricchia R, Magno M. Cytophagocytosis by the blast cells in acute myeloid leukemia. Leuk Lymphoma 1995;18(Suppl. 1):65. [2] Kurtin PJ, Dewald GW, Shields DJ, Hanson CA. Hematologic disorders associated with deletions of chromosome 20q: a clinicopathologic study of 107 patients. Am J Clin Pathol 1996;106:680.
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H. Mori et al. / Leukemia Research 24 (1999) 87–90
[3] Colon-Ortho G, Li CY, Dewald WG, White WL. Erythrophagocytic acute lymphocytic leukemia with B-cell markers and with a 20q − chromosome abnormality. Mayo Clin Proc 1984;59:67. [4] Jokhi PP, King A, Sharkey AM, Smith SK, Loke YW. Screening for cytokine messenger ribonucleic acid in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction. J Immunol 1994;153:4427. [5] Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C. Proposals for the recognition of minimally differentiated acute myeloid leukemia. Br J Haematol 1991;78:325. [6] Cuneo A, Ferrant A, Michaux JL, Boogaert M, Demuynck H, Orshoven AV, Criel A, Stul M, Cin PD, Hernandez J, Chatelain B, Doyen C, Louwagie A, Castoldi G, Cassiman JJ, Berghe HVD. Cytogenetic profile of minimally differentiated (FAB-M0) acute myeloid leukemia:correlation with clinicobiologic findings. Blood 1995;85:3688. [7] Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol 1997;65:215. [8] Laurencet FM, Chapuis B, Roux-Lombard P, Dayer JM, Beris Ph. Malignant histiocytosis in the leukemic stage:A new entity(M5c-AML) in the FAB Classification? Leukemia 1994;8:502. [9] Carter A, Haddad N, Draxler I, Israeli E, Raz B, Rowe JM. Expression and role in growth regulation of tumor necrosis
.
[10]
[11]
[12]
[13]
[14]
factor p55 and p75 in acute myeloblastic leukemia cells. Br J Haematol 1996;92:116. Kitagawa S, Yuo A, Yagisawa M, Azuma E, Yoshida, Furukawa Y, Takahashi M, Masuyama J, Takaku F. Activation of human monocyte functions by tumor necrosis factor: rapid priming for enhanced release of superoxiside and erythrophagocytosis, but no direct triggering of superoxide release. Exp Hematol 1996;24:559. Kuyama J, Fushino M, Take H, Kamayama Y. Myelodysplastic syndrome associated with erythrophagocytosis by blasts and myeloid cells. Int J Hematol 1995;62:243. Asimakopoulos FA, White NJ, Nacheva E, Green AR. Molecular analysis of chromosome 20q deletions associated with myeloproliferative disorders and myelodysplastic syndromes. Blood 1994;84:3086. Lai JL, Estinne MH, Fenaux P, Lepelley P, Huart JJ, Bauters F, Deminatti M. Translocation t(10;17)(p13;q12) in two cases of acute non lymphocytic leukemia with phagocytic activity of blasts. Cancer Genet Cytogenet 1989;39:45. Shimizu H, Ui T, Kawai S, Kaneko Y, Fujimoto T. Acute leukemia with active hemophagocytosis, positive immunologic markers for the megakaryocyte-platelet lineage, and translocation (16;21)(p11;q22). Jpn J Clin Hematol 1990;31:70.
Case report
Minimally differentiated acute myeloid leukemia (AML-M0) with extensive erythrophagocytosis and del(20)(q11) chromosome abnormality Hiroyuki Mori a,*, Masayuki Tawara a, Yoshiharu Yoshida b, Kazutaka Kuriyama a, Kazuyuki Sugahara c, Shimeru Kamihira c, Masao Tomonaga a a
Department of Hematology, Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki Uni6ersity School of Medicine, 1 -12 -4 Sakamoto, Nagasaki 852 -8102, Japan b Department of Internal Medicine, St. Francisco Hospital, Nagasaki, Japan c Department of Laboratory Medicine, Nagasaki Uni6ersity School of Medicine, Nagasaki, Japan Received 26 April 1999; accepted 12 July 1999
Abstract We describe an 84-year-old woman who presented severe pancytopenia and 36.6% of blasts accompanied with erythrophagocytosis in the bone marrow. According to cytochemical and immunological findings, a diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was established. Cytogenetic analysis revealed del(20)(q11) which were previously reported for one case each of ALL and MDS associated with cytophagocytosis by blasts, leading us to speculate a disease entity. Interestingly, a high expression of mRNA of TNF-a was detected by RT-PCR on the bone marrow mononuclear cells. © 1999 Elsevier Science Ltd. All rights reserved. Keywords: Acute myeloid leukemia; AML-M0; Cytophagocytosis; Deletion 20q; Tumor necrosis factor-a
1. Introduction Acute myeloid leukemia (AML) associated with cytophagocytosis by blast cells usually represent differentiated phenotypes of monocyte and/or granulocyte (M4/M5) [1], and also reported in M1, M2 and M7. Cytogenetic abnormalities in AML with cytophagocytosis reported in more than two cases were t(8;16)(p11;p13) and inv(8)(p11q13) in M4/M5, and t(16;21)(p11;q22). Other chromosomal abnormalities were reported sporadically. A terminal or interstitial deletion of the long arm of chromosome 20(20q− ) is one of the common chromosome abnormalities in myeloid disorders such as myelodysplastic syndrome (MDS), myeloproliferative disorders and AML [2]. Although it is a rare cytogenetic abnormality in acute lymphocytic leukemia (ALL), a case of ALL associated * Corresponding author. Fax: +81-95-8497113.
with del(20)(q11) was reported to have a striking erythrophagocytosis by blast cells [3].We here report a case of AML-M0 showing erythrophagocytosis and del(20)(q11).
2. Case report An 84-year-old woman was admitted to another hospital because of fever with chills and skin abscess. After admission severe pancytopenia and an increased number of abnormal cells associated with erythrophagocytosis in the bone marrow were found. Five years ago, when she had a operation for cataract, mild thrombocytopenia (platelets count of 117 109/l) was pointed out but no other hematological abnormality. The infection subsided which treatment with antibiotics and granulocyte-colony stimulating factor (G-CSF). Then she was referred to our hospital for further examination. On
0145-2126/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 1 4 5 - 2 1 2 6 ( 9 9 ) 0 0 1 4 5 - 9
88
H. Mori et al. / Leukemia Research 24 (1999) 87–90
physical examination, neither lymphoadenopathy nor hepatosplenomegaly was detected. Laboratory examination revealed hemoglobin 7.7 g/ dl, white blood cell count 0.6 /l with 1% blast, 0% granulocytes, 97% lymphocytes and 2% monocytes, and platelets count 33 /l. Coagulation tests were almost normal. The serum lactate dehydrogenase (LDH) level, serum and urine lysozyme were not elevated. Bone marrow aspiration revealed a mild hypocellular marrow, but megakaryocyts were preserved. Mature granulocytes were markedly decreased (1.2% of bone marrow nucleated cells), and erythroid cells were 24.8% of all nucleated cells and some of them had megaloblastoid changes. Blast cells were 36.6% in the marrow, which were highly variable in size and the morphological features, and some of them showing extensive erythrophagocytosis (Fig. 1). Mature monocytes were 0.45% of all nucleated cells. Staining for myeloperoxidase, chloroacetate esterase and butyrate esterase were all negative in the blast cells. Immunocytochmical staining and immunophenotyping by flowcytometory re-
vealed that most of the blast cells were positive for CD13, CD33 and HLA-DR, and negative for CD34, TdT, CD14,CD3, CD5, CD19, CD22, CD41, GPA, CD10 and MPO. Cytochemical and immunological findings were consistent with a diagnosis of AML-M0. On the bone marrow mononuclear cells, TCR and IgH rearrangements were not detected by PCR-SSCP (single strand conformation polymorphism). Cytogenetic analysis on the bone marrow cells showed del(20)(q11) in all metaphase analyzed, and 4/20 metaphase associated with + 21 (Fig. 2). The expression of cytokines was determined in mRNA level on the bone marrow mononuclear cells by RT-PCR. Total RNA was isolated from cell pellets by acid guanidinium thiocyanate–phenol–chloroform technique and treated by DNase. The cDNA was synthesized from 1 mg of total RNA using RNA PCR Core™ kit (Perkin-Elmer, NJ). PCR was carried out using following primers (hTNF-: Sense; 5%-ATGAGCATCGAAAGCATG-3%, Antisense; 5%TCACAGGGCAATGATCCC-3%) [4] and TaKaRa Ex Taq™ polymerase (Takara, Tokyo), and 30 cycles of amplification (95°C for 1 min, 55°C for 1 min, 72°C for 1 min). PCR products were electorophoresed on a 2% agarose gel and stained with ethidium bromide. A strong band of TNF-a was observed in patient (Fig. 3, lane 1) and thin band was identified in normal subject (lane 3). Furthermore to determine the level of TNF-a mRNA expression, a competitive PCR method using CytoXpress (Biosource International, California) for TNF- and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed. The ratio of copy number of TNF-a to GAPDH were 0.0479 in this patient and 0.0057 in normal subject (lane 3). The mRNA for FasL, IL-2 and IFN-g were not increased in this case compared with normal subjects (data not shown). Initially, because of no apparent growth of the leukemic cells and being asymptomatic, we administered only blood transfusion. As the disease progressed, the patient was treated with low dose cytosine arabinoside and aclarubicin, but it was not possible to have sufficient therapeutic effect. She died of pneumonia 6 months after the diagnosis.
3. Discussion
Fig. 1. Blasts from bone marrow of the patient. (A) Blasts showed the striking variability in morphology. Some had high nuclear/cytoplasmic ratio, others had low. Most of phagocyting blast cells showed scanty cytoplasm and no guranules (May-Grunwald Giemsa stain). (B) CD33 positive blasts by immunocytochemistory stain.
Cytochemical and immunological examinations did not reveal the features of differentiation towards either monocytes or granulocytes. According to the formulation of FAB classification system [5], we considered this case as minimally differentiated acute myeloid leukemia (AML-M0). It was reported that cytophagocytosis by leukemic blasts was observed in approximately 1% of all types of AML patients, and relatively frequent in monocytic types (M4, M5), but also seen in M1, M2
H. Mori et al. / Leukemia Research 24 (1999) 87–90
89
Fig. 2. Representative G-banded karyotype obtained from bone marrow. Arrow indicates deleted chromosome.
and M7. To our knowledge, there is no previous report of MO type AML presenting cytophagocytosis. This case seemed to be distinct from typical MO in terms of cell morphology and negativity of CD34 [6]. Moreover, we could not exclude completely a possibility of preceding MDS. Although the pathogenesis of phagocytosis is still unclear, some reports suggest association of several kinds of cytokines [7,8]. In our case, although the expression of mRNA of IL-2 and IFN-g were comparable with normal bone marrow, the expression of mRNA of TNF-a was greatly increased as detected by semi-quantitative RT-PCR on the bone marrow mononuclear cells. Though the origin of cells expressing TNF-a was unclear, it is likely that TNF-a contributed to the clinical features of cytophagocytosis in this case. In the previous reports, TNF-a was constitutively secreted by some AML cells, and acted as a growth stimulator of leukemic cells on some conditions [9]. TNF-a can also activate monocytes and enhance erythrophagocytosis [10]. It is known that a del(20q) is one of the common chromosome abnormalities in MDS, myeloproliferative disorders and AML, and the spectrum of these diseases led us to speculate that long arm of chromosome 20 represents the site of a tumor suppressor gene [2]. It was previously reported as a rare event that an ALL case associated with del(20)(q11) showed striking erythrophagocytosis by blast cells [3]. Furthermore, a case of MDS (refractory anemia with excess of blasts in transformation; RAEBt) who presented erythrophagocytosis had also del(20)(q12q13) abnormality [10]. Long arm of chromosome 20 is known to have several candidate tumor suppressor genes including hematopoietic cell kinase (hck) [11]; some functional genes that con-
Fig. 3. RT-PCR analysis of human TNF-a mRNA expression in marrow cells. Expression of TNF-a (upper column) and b-actin (lower column). Lane 1 represents this patient and lanes 2 and 3 represent normal subjects.
tribute to pathogenesis of those patients with cytophagocytosis might also exist in this region. Thus, our observation seems likely to suggest a disease entity which is characterized by cytophagocytosis by leukemic blasts and chromosome abnormality of 20q [12]. The 8p11 anomaly in M4/M5 is predominantly associated with cytophagocytosis, and also t(10;17)(p13;p12) [13] and t(16;21)(p11;q22) [14] were reported in M7 in relation to phagocytic properties. We emphasize the significance of 20q anomaly in cytophagocytosis because it appears to occur overriding cell lineages and clinical categories of leukemia.
References [1] Liso V, Specchia G, Capalbo S, Laricchia R, Magno M. Cytophagocytosis by the blast cells in acute myeloid leukemia. Leuk Lymphoma 1995;18(Suppl. 1):65. [2] Kurtin PJ, Dewald GW, Shields DJ, Hanson CA. Hematologic disorders associated with deletions of chromosome 20q: a clinicopathologic study of 107 patients. Am J Clin Pathol 1996;106:680.
90
H. Mori et al. / Leukemia Research 24 (1999) 87–90
[3] Colon-Ortho G, Li CY, Dewald WG, White WL. Erythrophagocytic acute lymphocytic leukemia with B-cell markers and with a 20q − chromosome abnormality. Mayo Clin Proc 1984;59:67. [4] Jokhi PP, King A, Sharkey AM, Smith SK, Loke YW. Screening for cytokine messenger ribonucleic acid in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction. J Immunol 1994;153:4427. [5] Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C. Proposals for the recognition of minimally differentiated acute myeloid leukemia. Br J Haematol 1991;78:325. [6] Cuneo A, Ferrant A, Michaux JL, Boogaert M, Demuynck H, Orshoven AV, Criel A, Stul M, Cin PD, Hernandez J, Chatelain B, Doyen C, Louwagie A, Castoldi G, Cassiman JJ, Berghe HVD. Cytogenetic profile of minimally differentiated (FAB-M0) acute myeloid leukemia:correlation with clinicobiologic findings. Blood 1995;85:3688. [7] Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol 1997;65:215. [8] Laurencet FM, Chapuis B, Roux-Lombard P, Dayer JM, Beris Ph. Malignant histiocytosis in the leukemic stage:A new entity(M5c-AML) in the FAB Classification? Leukemia 1994;8:502. [9] Carter A, Haddad N, Draxler I, Israeli E, Raz B, Rowe JM. Expression and role in growth regulation of tumor necrosis
.
[10]
[11]
[12]
[13]
[14]
factor p55 and p75 in acute myeloblastic leukemia cells. Br J Haematol 1996;92:116. Kitagawa S, Yuo A, Yagisawa M, Azuma E, Yoshida, Furukawa Y, Takahashi M, Masuyama J, Takaku F. Activation of human monocyte functions by tumor necrosis factor: rapid priming for enhanced release of superoxiside and erythrophagocytosis, but no direct triggering of superoxide release. Exp Hematol 1996;24:559. Kuyama J, Fushino M, Take H, Kamayama Y. Myelodysplastic syndrome associated with erythrophagocytosis by blasts and myeloid cells. Int J Hematol 1995;62:243. Asimakopoulos FA, White NJ, Nacheva E, Green AR. Molecular analysis of chromosome 20q deletions associated with myeloproliferative disorders and myelodysplastic syndromes. Blood 1994;84:3086. Lai JL, Estinne MH, Fenaux P, Lepelley P, Huart JJ, Bauters F, Deminatti M. Translocation t(10;17)(p13;q12) in two cases of acute non lymphocytic leukemia with phagocytic activity of blasts. Cancer Genet Cytogenet 1989;39:45. Shimizu H, Ui T, Kawai S, Kaneko Y, Fujimoto T. Acute leukemia with active hemophagocytosis, positive immunologic markers for the megakaryocyte-platelet lineage, and translocation (16;21)(p11;q22). Jpn J Clin Hematol 1990;31:70.