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Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: relation to morphology, age, sex and ethnicity - a single center study from Singapore

Enjeti AK, Tien SL, Sivaswaren CR

Hematol. J., 2004;5(5):419-25.
PMID: 15448668

Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity.

Matched MeSH terms: Leukemia, Myeloid/classification; Leukemia, Myeloid/genetics*; Leukemia, Myeloid/epidemiology; Leukemia, Myeloid/pathology
Immunoglobulin Heavy Chain Gene Rearrangement in Non B-cell Haematological Malignancies

Noor Haslina MN, Marini R, Rosnah B, Shafini MY, Wan Haslindawani WM, Mohd Nazri H, et al.

West Indian Med J, 2013 Nov;62(8):701-4.
PMID: 25014854 DOI: 10.7727/wimj.2013.253

OBJECTIVE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncology patients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia.
MEHTODS: We studied 18 cases of haematological malignancies which comprised five patients with T-ALL, 12 patients with AML and one with biphenotypic leukaemia.
RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement.
CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.

Matched MeSH terms: Leukemia, Myeloid, Acute
Fulltext Invasive aspergillosis in paediatric oncology patients

Muda Z, Ibrahim H, Abdulrahman EJ, Menon BS, Zahari Z, Zaleha AM, et al.

Med J Malaysia, 2008 Dec;63(5):415-6.
PMID: 19803305 MyJurnal

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Matched MeSH terms: Leukemia, Myeloid, Acute/microbiology*
Fulltext Malignant myeloid transformation in a child with severe congenital neutropenia (Kostmann's syndrome)

Chong LA, Josephine P, Ariffin H

Med J Malaysia, 2006 Jun;61(2):236-8.
PMID: 16898320 MyJurnal

We report a case of a child with severe congenital neutropenia (Kostmann's syndrome) who was treated with daily prophylactic subcutaneous granulocyte colony-stimulating factor (G-CSF) from the age of eight to sixteen years before being discontinued for poor haematological and clinical response. She did not have a HLA-matched sibling to enable bone marrow transplantation. She subsequently developed acute megakaryoblastic leukemia at the age of 17 years and succumbed during induction chemotherapy. The role of G-CSF in the pathogenesis of her malignant transformation to AML is complicated as this disorder has a propensity for myelodysplasia or AML as part of its natural history.

Matched MeSH terms: Leukemia, Myeloid/pathology*
Fulltext Varicella in children with haematological malignancy--outcome of treatment and prevention

Ho CM, Khuzaiah R, Yasmin AM

Med J Malaysia, 1994 Mar;49(1):29-35.
PMID: 8057987

Primary varicella-zoster virus infection in children with haematological malignancy is a life threatening disease. In one year, there were 10 cases of varicella and 2 cases of zoster among these children as well as 5 mothers who were accompanying their children who developed varicella in the oncology ward. Two children died of fulminating disease despite aggressive antiviral and supportive treatment. Acyclovir can be used in treatment and prophylaxis in exposed susceptible children. Varicella -zoster immune globulin is not available in this country. Vaccination with live virus has been shown to be protective in immunocompromised children and needs consideration.

Matched MeSH terms: Leukemia, Myeloid/complications*
Fulltext Leucostasis: an uncommon cause of respiratory distress

Goh KL, Bosco J, Wong CS

Med J Malaysia, 1983 Sep;38(3):194-6.
PMID: 6584709
Matched MeSH terms: Leukemia, Myeloid/blood; Leukemia, Myeloid/complications*
Fulltext Chromosome abnormalities in leukemia: a review

Chin YM, Hassan K

Med J Malaysia, 1984 Jun;39(2):103-11.
PMID: 6595495

The common chromosome abnormalities that are encountered in the various types of leukemia are discussed here. Chromosome abnormalities in leukemia are non-random and certain chromosomal changes are now becoming recognised as being rather specific for certain leukemia types.

Matched MeSH terms: Leukemia, Myeloid/genetics
Fulltext Scopulariopsis brevicaulis infection in a patient with acute myeloid leukemia

Ng KP, Soo-Hoo TS, Na SL, Gan GG, Sangkar JV, Teh AKH

Med J Malaysia, 2003 Oct;58(4):608-12.
PMID: 15190640

Scopulariopsis brevicaulis is a soil fungus normally associated with onychomycosis. It causes subcutaneous infection in immunocompromised patients and is rarely isolated from blood. A case of systemic Scopulariopsis brevicaulis infection was reported in a patient with acute myeloid leukemia. The patient developed persistent fever that did not respond to wide spectrum antibiotics and amphotericin B. Scopulariopsis brevicaulis was the only pathogen isolated from blood cultures. The fever subsided with itraconazole and there was no recurrence of fungal infection with prolonged maintenance of oral itraconazole.

Matched MeSH terms: Leukemia, Myeloid/complications*
Fulltext Allogeneic haemopoietic stem cell transplantation using non-myeloablative conditioning--a local experience

Leong CF, Cheong SK, Fadilah SAW, Ainoon O, Hamidah NH

Med J Malaysia, 2003 Jun;58(2):229-35.
PMID: 14569743

Allogeneic haemopoietic stem cell transplantation was initially considered as a means of delivering supralethal doses of chemotherapy with or without total body irradiation for the treatment of malignancy. However, it has become clear that this mode of therapy does not eradicate the malignancy in many patients and its benefit is largely due to the immune mediated graft versus malignancy effect. This has led to development of alternative strategy to utilize a less intensive preparative regimen pre-transplantation that provides sufficient immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus allowing the evolution of a graft versus malignancy effect post-transplantation. Since September 1999, we had carried out 10 cases of allogeneic peripheral blood stem cell transplantation: one case of aplastic anaemia, four cases of acute myeloid leukemia (AML) in first remission, and five cases of chronic myeloid leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from transplantation was rapid with no or brief period of neutropenia or thrombocytopenia. Engraftment was established by determining donor's short tandem repeats in the recipient's bone marrow at day 30, 60 and 100 post-transplantation. Seven cases (70%) show partial or complete donor's chimerism by day 30 indicating successful engraftment. No treatment mortality was noted at day 100. Graft versus host disease was generally limited. Up to the date of reporting, two patients with CML had graft failure, one was successfully re-transplanted later. Two patients with AML had since relapsed and passed away. The others remain alive and well. The cost of transplantation on average was estimated to be about a quarter of that using a myeloablative regimen. It appears that this treatment strategy is a promising approach for the management of blood disorders.

Matched MeSH terms: Leukemia, Myeloid, Acute/therapy*
Prognostic significance of morphological and cytochemical markers in adult acute myelogenous leukaemia: concepts and observations

George E, Kamarulzaman E

Med J Malaysia, 1979 Dec;34(2):184-6.
PMID: 297198
Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis; Leukemia, Myeloid, Acute/pathology*
A case of modified A antigen in acute leukaemia

Antoni A, Case J

Med J Malaysia, 1974 Jun;28(4):290-2.
PMID: 4278976
Matched MeSH terms: Leukemia, Myeloid, Acute/immunology*
Uncontrollable bleeding due to hypofibrinogenemia in a case of acute myelo-monocytic leukaemia

Banerjee AK

Med J Malaya, 1971 Mar;25(3):187-92.
PMID: 4253245
Matched MeSH terms: Leukemia, Myeloid, Acute/complications*
Fulltext Molecular responses during chemotherapy in acute myeloid leukemias in predicting poor-response to standard chemotherapy

Maha A, Cheong SK, Leong CF, Seow HF

Malays J Pathol, 2009 Dec;31(2):81-91.
PMID: 20514850 MyJurnal

Signal transduction pathways are constitutively expressed in leukaemic cells resulting in aberrant survival of the cells. It is postulated that in cells of chemo-sensitive patients, chemotherapy induces apoptotic signals leading to cell death while survival signals are maintained in cells of chemo-resistant patients. There is very little information currently, on the expression of these mediators in patients immediately after chemotherapy initiation. We examined the expression pattern of proinflammatory cytokines, signaling molecules of the PI3K and MAPK pathways molecules and death receptor, DR5 on paired samples at diagnosis and during chemotherapy in acute myeloid leukaemia patients treated with cytosine arabinoside and daunorubicin. The results were correlated with remission status one month after chemotherapy. We found that in chemo-sensitive patients, chemotherapy significantly increased the percentage of cases expressing TNF-alpha (p = 0.025, n = 9) and IL-6 (p = 0.002, n = 11) compared to chemo-resistant cases. We also observed an increased percentage of chemo-sensitive cases expressing DR5 and phosphorylated p38, and Jnk. Thus, expression of TNF-alpha, IL-6, DR5, phospho-p38 and phospho-Jnk may regulate cell death in chemo-sensitive cases. In contrast, a significantly higher percentage of chemo-resistant cases expressed phospho-Bad (p = 0.027, n = 9). IL-beta and IL-18 were also found to be higher in chemo-resistant cases at diagnosis and during chemotherapy. Thus, expression of various cellular molecules in leukaemic blasts during chemotherapy may be useful in predicting treatment outcome. These cellular molecules may also be potential targets for alternative therapy.

Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/genetics; Leukemia, Myeloid, Acute/pathology
Fulltext Experimental production of clinical-grade dendritic cell vaccine for acute myeloid leukemia

Tan YF, Sim GC, Habsah A, Leong CF, Cheong SK

Malays J Pathol, 2008 Dec;30(2):73-9.
PMID: 19291915 MyJurnal

Dendritic cells (DC) are professional antigen presenting cells of the immune system. Through the use of DC vaccines (DC after exposure to tumour antigens), cryopreserved in single-use aliquots, an attractive and novel immunotherapeutic strategy is available as an option for treatment. In this paper we describe an in vitro attempt to scale-up production of clinical-grade DC vaccines from leukemic cells. Blast cells of two relapsed AML patients were harvested for DC generation in serum-free culture medium containing clinical-grade cytokines GM-CSF, IL-4 and TNF-alpha. Cells from patient 1 were cultured in a bag and those from patient 2 were cultured in a flask. The numbers of seeding cells were 2.24 x 10(8) and 0.8 x 10(8), respectively. DC yields were 10 x 10(6) and 29.8 x 10(6) cells, giving a conversion rate of 4.7% and 37%, respectively. These DC vaccines were then cryopreserved in approximately one million cells per vial with 20% fresh frozen group AB plasma and 10% DMSO. At 12 months and 21 months post cryopreservation, these DC vaccines were thawed, and their sterility, viability, phenotype and functionality were studied. DC vaccines remained sterile up to 21 months of storage. Viability of the cryopreserved DC in the culture bag and flask was found to be 50% and 70% at 12 months post cryopreservation respectively; and 48% and 67% at 21 months post cryopreservation respectively. These DC vaccines exhibited mature DC surface phenotypic markers of CD83, CD86 and HLA-DR, and negative for haemopoietic markers. Mixed lymphocyte reaction (MLR) study showed functional DC vaccines. These experiments demonstrated that it is possible to produce clinical-grade DC vaccines in vitro from blast cells of leukemic patients, which could be cryopreserved up to 21 months for use if repeated vaccinations are required in the course of therapy.

Matched MeSH terms: Leukemia, Myeloid, Acute/immunology*; Leukemia, Myeloid, Acute/therapy
Assessment of P-gp and MRP1 activities using MultiDrugQuant Assay Kit: a preliminary study of correlation between protein expressions and its functional activities in newly diagnosed acute leukaemia patients

Fazlina N, Maha A, Zarina AL, Hamidah A, Zulkifli SZ, Cheong SK, et al.

Malays J Pathol, 2008 Dec;30(2):87-93.
PMID: 19291917

Multidrug resistance (MDR) is believed to be responsible for poor response of patients towards chemotherapy particularly patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The best-characterized resistance mechanism is the one mediated by permeability-glycoprotein (P-gp) encoded by MDR1 gene, which is responsible for drug efflux. We studied P-gp and multidrug resistance-associated protein 1 (MRP1) expression and functional activities in 43 newly diagnosed acute leukemia cases (19 paediatric ALL cases and 24 adult AML cases). The expression and functional activities were examined using flow cytometry and MultiDrugQuant assay kit (involving calcein AM uptake and efflux). P-gp and MRP1 expression and its functional activities were observed in 68.4% of paediatric ALL. In adult AML cases, all cases expressed MRP1 and its functional activities but only 58.3% were positive for P-gp and its functional activities. We were able to show a significant correlation between the expression of the multidrug resistant protein (P-gp and MRP1) and their functional activity in adult AML and paediatric ALL samples.

Matched MeSH terms: Leukemia, Myeloid, Acute/metabolism*
Fulltext Herpes zoster in children with cancer

Menon BS, Wan Maziah WM

Malays J Pathol, 2001 Jun;23(1):47-8.
PMID: 16329548

The aim of this study was to determine the incidence and outcome of herpes zoster hospitalised children with cancer in Kota Baru. It was a retrospective review from January 1994 to December 1998. The diagnosis of herpes zoster was a clinical one. Herpes zoster was diagnosed in 10 of 188 (5%) children with malignancy. The most common malignancy was leukaemia. Nine children were treated with acyclovir. No child developed visceral dissemination and there were no deaths.

Matched MeSH terms: Leukemia, Myeloid, Acute/immunology; Leukemia, Myeloid, Acute/epidemiology; Leukemia, Myeloid, Acute/virology*
Fulltext Generation of dendritic cells from acute myeloid leukaemia cells and monocytes: our local experience

Lim MN, Leong CF, Cheong SK, Seow HF

Malays J Pathol, 2003 Dec;25(2):107-12.
PMID: 16196366

Dendritic cells (DC) are efficient and potent antigen-presenting cells. Pilot clinical trials indicated that DC loaded with tumour antigen could induce tumour-specific immune responses in various cancers including B-cell lymphoma, melanoma and prostate cancer. Owing to extensively low number of DC in the blood circulation, a variety of sources have been used to generate DC including monocytes, CD34+ stem cells and even with leukaemic blast cells. We demonstrate here a simple method to generate DC from acute myeloid leukaemia (AML) cells and monocytes from healthy donor or remission samples. AML cells or monocytes were cultured in RPMI 1640 media supplemented with foetal bovine serum or autologous serum where possible and different combinations of cytokines GM-CSF, IL-4 and TNF-alpha. The generated DC were evaluated for their morphology by phase contrast microscopy and May Grunwald Giemsa staining. Viability of cells was determined by trypan blue dye exclusion. Percentage of yields and immunophenotypes were carried out by flow cytometry. We found that cultured AML cells and monocytes developed morphological and immuno-phenotypic characteristics of DC. Monocytes are better than AML blast in generating DC and serve as a ready source for dendritic cell vaccine development.

Matched MeSH terms: Leukemia, Myeloid, Acute/immunology*; Leukemia, Myeloid, Acute/pathology
Biphenotypic hybrid acute leukaemia detected by two colour flow cytometry

Gudum HR, Chin YM, Menaka N, Jeyaranee S, Lin HP, Tay A

Malays J Pathol, 1992 Jun;14(1):25-8.
PMID: 1469914

Immunophenotypic studies using immunofluorescent flow cytometry were performed on the blast cells of 36 patients with acute leukaemia using a panel of eight monoclonal antibodies. Six patients had blasts which co-expressed markers for lymphoid and myeloid differentiation, and which were therefore defined as biphenotypic hybrid acute leukaemia. Of the six, three patients were in the paediatric age group (below 12 years old) while the other three were more than 12 years old. Peripheral blood counts were variable; however, bone marrow infiltration was extensive (blasts > or = 75% in all). At the time of study, remission was achieved in only two patients. The authors' data show that biphenotypic hybrid acute leukaemia is not rare in Malaysia. This represents a subgroup of acute leukaemia identifiable by immunophenotyping but not by the French-American-British classification based on morphological and basic cytochemical studies alone. The recognition of this subgroup is important for both practical and theoretical reasons. There are implications for treatment of the individual patient because treatment directed at a single lineage may not be effective. The two colour flow cytometry proved to be a useful tool for diagnosis and classification of acute leukaemia.

Matched MeSH terms: Leukemia, Myeloid, Acute/classification; Leukemia, Myeloid, Acute/pathology*
Single incubation double esterase cytochemical reaction using a single coupling reagent

Ainoon O, Jabamoney AJ, Cheong SK

Malays J Pathol, 1991 Jun;13(1):47-9.
PMID: 1724544

Most methods used in double esterase cytochemistry for the diagnosis and classification of acute myeloid leukaemias require double incubation and staining, using separate coupling reagents. We evaluated a method by Swirsky on our normal and abnormal blood and bone marrow smears where only a single incubation and the use of a single coupling reagent is required. Its short incubation period and its strong positive reaction for butyrate esterase in demonstrating cells of monocytic lineage gives it an advantage over the conventional double incubation technique.

Matched MeSH terms: Leukemia, Myeloid/diagnosis*; Leukemia, Myeloid/enzymology
Selection of reference genes for quantitative studies in acute myeloid leukaemia

Lee C, Yiau KXS, Lee LJ, Chong PP, Chang KM, Abdullah M

Malays J Pathol, 2019 Dec;41(3):313-326.
PMID: 31901916

INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed.
MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12).
RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns.
CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.

Matched MeSH terms: Leukemia, Myeloid, Acute/genetics*

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